36 results on '"Germán Domínguez-Vías"'
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2. Correlational Study of Aminopeptidase Activities between Left or Right Frontal Cortex versus the Hypothalamus, Pituitary, Adrenal Axis of Spontaneously Hypertensive Rats Treated with Hypotensive or Hypertensive Agents
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Isabel Prieto, Ana Belén Segarra, Inmaculada Banegas, Magdalena Martínez-Cañamero, Raquel Durán, Francisco Vives, Germán Domínguez-Vías, and Manuel Ramírez-Sánchez
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brain asymmetry ,neuro-endocrine asymmetry ,neuro-visceral integration ,hypertension ,renin–angiotensin system ,aminopeptidases ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
It has been suggested that the neuro-visceral integration works asymmetrically and that this asymmetry is dynamic and modifiable by physio-pathological influences. Aminopeptidases of the renin–angiotensin system (angiotensinases) have been shown to be modifiable under such conditions. This article analyzes the interactions of these angiotensinases between the left or right frontal cortex (FC) and the same enzymes in the hypothalamus (HT), pituitary (PT), adrenal (AD) axis (HPA) in control spontaneously hypertensive rats (SHR), in SHR treated with a hypotensive agent in the form of captopril (an angiotensin-converting enzyme inhibitor), and in SHR treated with a hypertensive agent in the form of the L-Arginine hypertensive analogue L-NG-Nitroarginine Methyl Ester (L-NAME). In the control SHR, there were significant negative correlations between the right FC with HPA and positive correlations between the left FC and HPA. In the captopril group, the predominance of negative correlations between the right FC and HPA and positive correlations between the HPA and left FC was maintained. In the L-NAME group, a radical change in all types of interactions was observed; particularly, there was an inversion in the predominance of negative correlations between the HPA and left FC. These results indicated a better balance of neuro-visceral interactions after captopril treatment and an increase in these interactions in the hypertensive animals, especially in those treated with L-NAME.
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- 2023
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3. Physiological effects in a microgravity environment
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Isabel Prieto-Gómez, Manuel Ramirez-Sánchez, and Germán Domínguez-Vías
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Medicine (General) ,R5-920 - Published
- 2021
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4. Asymmetric Pattern of Correlations of Leucine Aminopeptidase Activity between Left or Right Frontal Cortex versus Diverse Left or Right Regions of Rat Brains
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Manuel Ramírez-Sánchez, Isabel Prieto, Ana Belén Segarra, Inmaculada Banegas, Magdalena Martínez-Cañamero, Germán Domínguez-Vías, Raquel Durán, Francisco Vives, and Francisco Alba
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brain asymmetry ,intra-hemispheric correlations ,inter-hemispheric correlations ,leucine aminopeptidase ,lactate dehydrogenase ,brain heterogeneity ,Mathematics ,QA1-939 - Abstract
Previous studies demonstrated an asymmetry of left predominance for mean values of soluble leucine aminopeptidase (LeuAP) activity in the frontal cortex (FC) and hypothalamus of adult male rats, fluorimetrically analyzed by the hydrolysis of Leu-β-naphthylamide as a substrate. No asymmetries were observed in nine other left (L) and right (R) regions obtained from rostro-caudally sectioned coronal slices. Neither had inter-hemispheric differences observed for lactate dehydrogenase (LDH), analyzed simultaneously in the same brain regions (L and R) of the same animals. However, the level of intra-hemispheric or inter-hemispheric correlation of LeuAP or LDH between such brain regions has not been analyzed. In order to obtain additional suggestions on the functional heterogeneity between regions of LeuAP and LDH, in the present investigation, the level of intra-hemispheric and inter-hemispheric correlations of the frontal cortex with the rest of the regions studied is described: (A) between the left frontal cortex (LFC) and the rest of the left regions; (B) between the right frontal cortex (RFC) and the rest of the right regions; (C) between the left frontal cortex and all of the right regions; and (D) between the right frontal cortex and all of the left regions. All of the correlations obtained were positive. The intra-hemispheric analysis showed a greater heterogeneity of values in the correlations observed between RFC and the rest of the right regions than between LFC and the rest of the left regions. Greater heterogeneity is observed when comparing RFC correlations with left regions than when comparing LFC correlations with right regions. In conclusion, the greatest heterogeneity (suggesting a greater functional variability) was observed in the right intra-hemispheric analysis and in the inter-hemispheric analysis between the RFC and the left hemisphere. The results for LDH showed a great homogeneity between regions both in the intra- and inter-hemispheric studies.
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- 2023
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5. Systematic Review and Meta-Analyses of Aminopeptidases as Prognostic Biomarkers in Amyotrophic Lateral Sclerosis
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Bárbara Teruel-Peña, José Luís Gómez-Urquiza, Nora Suleiman-Martos, Isabel Prieto, Francisco José García-Cózar, Manuel Ramírez-Sánchez, Carmen Fernández-Martos, and Germán Domínguez-Vías
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amyotrophic lateral sclerosis ,aminopeptidase ,biomarker ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the progressive loss of motor neurons in the spinal cord, brain stem, and cerebral cortex. Biomarkers for ALS are essential for disease detection and to provide information on potential therapeutic targets. Aminopeptidases catalyze the cleavage of amino acids from the amino terminus of protein or substrates such as neuropeptides. Since certain aminopeptidases are known to increase the risk of neurodegeneration, such mechanisms may reveal new targets to determine their association with ALS risk and their interest as a diagnostic biomarker. The authors performed a systematic review and meta-analyses of genome-wide association studies (GWASs) to identify reported aminopeptidases genetic loci associated with the risk of ALS. PubMed, Scopus, CINAHL, ISI Web of Science, ProQuest, LILACS, and Cochrane databases were searched to retrieve eligible studies in English or Spanish, published up to 27 January 2023. A total of 16 studies were included in this systematic review, where a series of aminopeptidases could be related to ALS and could be promising biomarkers (DPP1, DPP2, DPP4, LeuAP, pGluAP, and PSA/NPEPPS). The literature reported the association of single-nucleotide polymorphisms (SNPs: rs10260404 and rs17174381) with the risk of ALS. The genetic variation rs10260404 in the DPP6 gene was identified to be highly associated with ALS susceptibility, but meta-analyses of genotypes in five studies in a matched cohort of different ancestry (1873 cases and 1861 control subjects) showed no ALS risk association. Meta-analyses of eight studies for minor allele frequency (MAF) also found no ALS association for the “C” allele. The systematic review identified aminopeptidases as possible biomarkers. However, the meta-analyses for rs1060404 of DPP6 do not show a risk associated with ALS.
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- 2023
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6. Bombarderos en picado (1941): un modelo de estudio de la fisiología de la aviación
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Germán Domínguez-Vías
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altitud ,hipoxia hipobárica ,síncope ,aviación ,Medicine (General) ,R5-920 - Abstract
Este artículo sirve para iniciarse en las bases docentes de la actual fisiología de la aviación, cuyo origen se remonta al comienzo de la Segunda Guerra Mundial. Bombarderos en picado (1941) de Michael Curtiz es un excelente material docente para ayudar en la comprensión de las distintas causas del síncope de los pilotos en las alturas, permitiendo la reflexión y la búsqueda de soluciones o alternativas a través de experimentos que permiten la recuperación de la homeostasis corporal. Su material audiovisual comparte escenas reales del ejército americano que permiten acceder a estos descubrimientos y al avance del estado actual de la moderna fisiología aeroespacial.
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- 2020
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7. Aminopeptidase Activities Interact Asymmetrically between Brain, Plasma and Systolic Blood Pressure in Hypertensive Rats Unilaterally Depleted of Dopamine
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Inmaculada Banegas, Isabel Prieto, Ana Belén Segarra, Francisco Vives, Magdalena Martínez-Cañamero, Raquel Durán, Juan de Dios Luna, Germán Domínguez-Vías, and Manuel Ramírez-Sánchez
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dopamine ,limbic system ,medial prefrontal cortex ,hippocampus ,amygdala ,brain asymmetry ,Biology (General) ,QH301-705.5 - Abstract
Brain dopamine, in relation to the limbic system, is involved in cognition and emotion. These functions are asymmetrically processed. Hypertension not only alters such functions but also their asymmetric brain pattern as well as their bilateral pattern of neurovisceral integration. The central and peripheral renin-angiotensin systems, particularly the aminopeptidases involved in its enzymatic cascade, play an important role in blood pressure control. In the present study, we report how these aminopeptidases from left and right cortico-limbic locations, plasma and systolic blood pressure interact among them in spontaneously hypertensive rats (SHR) unilaterally depleted of dopamine. The study comprises left and right sham and left and right lesioned (dopamine-depleted) rats as research groups. Results revealed important differences in the bilateral behavior comparing sham left versus sham right, lesioned left versus lesioned right, and sham versus lesioned animals. Results also suggest an important role for the asymmetrical functioning of the amygdala in cardiovascular control and an asymmetrical behavior in the interaction between the medial prefrontal cortex, hippocampus and amygdala with plasma, depending on the left or right depletion of dopamine. Compared with previous results of a similar study in Wistar-Kyoto (WKY) normotensive rats, the asymmetrical behaviors differ significantly between both WKY and SHR strains.
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- 2022
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8. Sp1-regulated expression of p11 contributes to motor neuron degeneration by membrane insertion of TASK1
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Victoria García-Morales, Guillermo Rodríguez-Bey, Laura Gómez-Pérez, Germán Domínguez-Vías, David González-Forero, Federico Portillo, Antonio Campos-Caro, Ángela Gento-Caro, Noura Issaoui, Rosa M. Soler, Ana Garcera, and Bernardo Moreno-López
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Science - Abstract
The adaptor protein p11 and K+ channel TASK1 have overlapping distributions in the CNS. Here, the authors demonstrate that the transcription factor Sp1 regulates p11 levels, which in turn affects intrinsic membrane properties and can contribute to degeneration of motor neurons in disease and injury models.
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- 2019
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9. Asymmetric Interaction of Neuropeptidase Activities between Cortico-Limbic Structures, Plasma and Cardiovascular Function after Unilateral Dopamine Depletions of the Nigrostriatal System
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Inmaculada Banegas, Isabel Prieto, Ana Belén Segarra, Francisco Vives, Magdalena Martínez-Cañamero, Raquel Durán, Juan de Dios Luna, Marc de Gasparo, Germán Domínguez-Vías, and Manuel Ramírez-Sánchez
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neuropeptides ,neuropeptidases ,neurochemical asymmetry ,functional asymmetry ,neurovisceral integration ,Biology (General) ,QH301-705.5 - Abstract
In emotional processing, dopamine (DA) plays an essential role, and its deterioration involves important consequences. Under physiological conditions, dopamine exhibits brain asymmetry and coexists with various neuropeptides that can coordinate the processing of brain functions. Brain asymmetry can extend into a broader concept of asymmetric neurovisceral integration, including behavior. The study of the activity of neuropeptide regulatory enzymes (neuropeptidases, NPs) is illustrative. We have observed that the left and right brain areas interact intra- and inter-hemispherically, as well as with peripheral tissues or with physiological parameters such as blood pressure or with behaviors such as turning preference. To obtain data that reflect this integrative behavior, we simultaneously analyzed the impact of left or right brain DA depletion on the activity of various NPs in corticolimbic regions of the left and right hemispheres, such as the medial prefrontal cortex, amygdala and hippocampus, as well as on the plasma activity of the same aminopeptidase activities (APs) and on systolic blood pressure (SBP). Intra- and inter-hemispheric interactions as well as the interactions of NPs from the left or right hemispheres were analyzed with the same plasma APs and the SBP obtained from sham and from left or right lesioned rats. The results demonstrate a complex profile depending on the hemisphere considered. They definitively confirm an asymmetric neurovisceral integration and reveal a higher level of inter-hemispheric corticolimbic interactions including with SBP after left dopamine depletion.
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- 2022
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10. Brain Asymmetry: Towards an Asymmetrical Neurovisceral Integration
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Manuel Ramírez-Sánchez, Isabel Prieto, Ana Belén Segarra, Inmaculada Banegas, Magdalena Martínez-Cañamero, Germán Domínguez-Vías, and Marc de Gasparo
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neurochemical asymmetry ,functional asymmetry ,neurovisceral integration ,neuropeptides ,neuropeptidases ,Mathematics ,QA1-939 - Abstract
Despite the ancestral evidence of an asymmetry in motor predominance, going through the inspiring discoveries of Broca and Wernicke on the localization of language processing, continuing with the subsequent noise coinciding with the study of brain function in commissurotomized patients—and the subsequent avalanche of data on the asymmetric distribution of multiple types of neurotransmitters in physiological and pathological conditions—even today, the functional significance of brain asymmetry is still unknown. Currently, multiple evidence suggests that functional asymmetries must have a neurochemical substrate and that brain asymmetry is not a static concept but rather a dynamic one, with intra- and inter-hemispheric interactions between its various processes, and that it is modifiable depending on changing endogenous and environmental conditions. Furthermore, based on the concept of neurovisceral integration in the overall functioning of an organism, some evidence has emerged suggesting that this integration could be organized asymmetrically, using the autonomic nervous system as a bidirectional communication pathway, whose performance would also be asymmetric. However, the functional significance of this distribution, as well as the evolutionary advantage of an asymmetric nervous organization, is still unknown.
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- 2021
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11. The Type of Fat in the Diet Influences Regulatory Aminopeptidases of the Renin-Angiotensin System and Stress in the Hypothalamic-Pituitary-Adrenal Axis in Adult Wistar Rats
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Germán Domínguez-Vías, Ana Belén Segarra, Manuel Ramírez-Sánchez, and Isabel Prieto
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aminopeptidase ,angiotensinase ,dipeptidyl peptidase IV ,high-fat diet ,hypothalamus-pituitary-adrenal axis ,renin-angiotensin system ,Nutrition. Foods and food supply ,TX341-641 - Abstract
(1) Background: Prolonged feeding with a high-fat diet (HFD) acts as a stressor by activating the functions of the hypothalamic-pituitary-adrenal gland (HPA) stress axis, accompanied of hypertension by inducing the renin-angiotensin-aldosterone system. Angiotensinases enzymes are regulatory aminopeptidases of angiotensin metabolism, which together with the dipeptidyl peptidase IV (DPP-IV), pyroglutamyl- and tyrosyl-aminopeptidase (pGluAP, TyrAP), participate in cognitive, stress, metabolic and cardiovascular functions. These functions appear to be modulated by the type of fat used in the diet. (2) Methods: To analyze a possible coordinated response of aminopeptidases, their activities were simultaneously determined in the hypothalamus, adenohypophysis and adrenal gland of adult male rats fed diets enriched with monounsaturated (standard diet (S diet) supplemented with 20% virgin olive oil; VOO diet) or saturated fatty acids (diet S supplemented with 20% butter and 0.1% cholesterol; Bch diet). Aminopeptidase activities were measured by fluorimetry using 2-Naphthylamine as substrates. (3) Results: the hypothalamus did not show differences in any of the experimental diets. In the pituitary, the Bch diet stimulated the renin-angiotensin system (RAS) by increasing certain angiotensinase activities (alanyl-, arginyl- and cystinyl-aminopeptidase) with respect to the S and VOO diets. DPP-IV activity was increased with the Bch diet, and TyrAP activity decrease with the VOO diet, having both a crucial role on stress and eating behavior. In the adrenal gland, both HFDs showed an increase in angiotensinase aspartyl-aminopeptidase. The interrelation of angiotensinases activities in the tissues were depending on the type of diet. In addition, correlations were shown between angiotensinases and aminopeptidases that regulate stress and eating behavior. (4) Conclusions: Taken together, these results support that the source of fat in the diet affects several peptidases activities in the HPA axis, which could be related to alterations in RAS, stress and feeding behavior.
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- 2021
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12. High-Fat Diets Modify the Proteolytic Activities of Dipeptidyl-Peptidase IV and the Regulatory Enzymes of the Renin–Angiotensin System in Cardiovascular Tissues of Adult Wistar Rats
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Germán Domínguez-Vías, Ana Belén Segarra, Manuel Ramírez-Sánchez, and Isabel Prieto
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aminopeptidase activities ,angiotensinases ,dipeptidyl peptidase IV ,high-fat diet ,virgin olive oil ,Biology (General) ,QH301-705.5 - Abstract
(1) Background: The replacement of diets high in saturated fat (SAFA) with monounsaturated fatty acids (MUFA) is associated with better cardiovascular function and is related to the modulation of the activity of the local renin–angiotensin system (RAS) and the collagenase activity of dipeptidyl peptidase IV (DPP-IV). The objective of the work was to verify the capacity of different types of dietary fat on the regulatory activities of RAS and DPP-IV. (2) Methods: Male Wistar rats were fed for 24 weeks with three different diets: the standard diet (S), the standard diet supplemented with virgin olive oil (20%) (VOO), or with butter (20%) plus cholesterol (0.1%) (Bch). The proteolytic activities were determined by fluorometric methods in the soluble (sol) and membrane-bound (mb) fractions of the left ventricle and atrium, aorta, and plasma samples. (3) Results: With the VOO diet, angiotensinase values were significantly lower than with the Bch diet in the aorta (GluAP and ArgAP (mb)), ventricle (ArgAP (mb)) and atrium (CysAP (sol)). Significant decreases in DPP-IV (mb) activity occurred with the Bch diet in the atrium and aorta. The VOO diet significantly reduced the activity of the cardiac damage marker LeuAP (mb) in the ventricle and aorta, except for LeuAP (sol) in the ventricle, which was reduced with the Bch diet. (4) Conclusions: The introduction into the diet of a source rich in MUFA would have a beneficial cardiovascular effect on RAS homeostasis and cardiovascular functional stability.
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- 2021
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13. Interaction between Angiotensinase Activities in Pituitary and Adrenal Glands of Wistar–Kyoto and Spontaneously Hypertensive Rats under Hypotensive or Hypertensive Treatments
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Ana B. Segarra, Isabel Prieto, Inmaculada Banegas, Magdalena Martínez-Cañamero, Ana B. Villarejo, Germán Domínguez-Vías, Marc de Gasparo, and Manuel Ramírez-Sánchez
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aminopeptidases ,Wistar–Kyoto ,spontaneously hypertensive rats ,pituitary ,adrenals ,captopril ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
In the present study, we analyzed the activity of several aminopeptidases (angiotensinases) involved in the metabolism of various angiotensin peptides, in pituitary and adrenal glands of untreated Wistar–Kyoto (WKY) and spontaneously hypertensive rats (SHR) or treated with the antihypertensive drugs captopril and propranolol or with the L-Arginine hypertensive analogue L-NG-Nitroarginine Methyl Ester (L-NAME). Intra- and inter-gland correlations between angiotensinase activities were also calculated. Membrane-bound alanyl-, cystinyl-, and glutamyl-aminopeptidase activities were determined fluorometrically using aminoacyl-β-naphthylamide as substrates. Depending on the type of angiotensinase analyzed, the results reflect a complex picture showing substantial differences between glands, strains, and treatments. Alanyl-aminopeptidase responsible for the metabolism of Ang III to Ang IV appears to be the most active angiotensinase in both pituitary and adrenals of WKY and particularly in SHR. Independently of treatment, most positive correlations are observed in the pituitary gland of WKY whereas such positive correlations are predominant in adrenals of SHR. Negative inter-gland correlations were observed in control SHR and L-NAME treated WKY. Positive inter-gland correlations were observed in captopril-treated SHR and propranolol-treated WKY. These results may reflect additional mechanisms for increasing or decreasing systolic blood pressure in WKY or SHR.
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- 2021
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14. Effects of Virgin Olive Oil on Blood Pressure and Renal Aminopeptidase Activities in Male Wistar Rats
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Germán Domínguez-Vías, Ana Belén Segarra, Manuel Ramírez-Sánchez, and Isabel Prieto
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renal–aminopeptidase activities ,systolic blood pressure ,high-fat diet ,virgin olive oil ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
High saturated fat diets have been associated with the development of obesity and hypertension, along with other pathologies related to the metabolic syndrome. In contrast, the Mediterranean diet, characterized by its high content of monounsaturated fatty acids, has been proposed as a dietary factor capable of positively regulating cardiovascular function. These effects have been linked to changes in the local renal renin angiotensin system (RAS) and the activity of the sympathetic nervous system. The main goal of this study was to analyze the role of two dietary fat sources on aminopeptidases activities involved in local kidney RAS. Male Wistar rats (six months old) were fed during 24 weeks with three different diets: the standard diet (S), the standard diet supplemented with virgin olive oil (20%) (VOO), or the standard diet enriched with butter (20%) plus cholesterol (0.1%) (Bch). Kidney samples were separated in medulla and cortex for aminopeptidase activities (AP) assay. Urine samples were collected for routine analysis by chemical tests. Aminopeptidase activities were determined by fluorometric methods in soluble (sol) and membrane-bound (mb) fractions of renal tissue, using arylamide derivatives as substrates. After the experimental period, the systolic blood pressure (SBP) values were similar in standard and VOO animals, and significantly lower than in the Bch group. At the same time, a significant increase in GluAP and IRAP activities were found in renal medulla of Bch animals. However, in VOO group the increase of GluAP activity in renal medulla was lower, while AspAP activity decreased in the renal cortex. Furthermore, the VOO diet also affected other aminopeptidase activities, such as TyrAP and pGluAP, related to the regulation of the sympathetic nervous system and the metabolic rate. These results support the beneficial effect of VOO in the regulation of SBP through changes in local AP activities of the kidney.
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- 2021
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15. Hypothalamic Renin–Angiotensin System and Lipid Metabolism: Effects of Virgin Olive Oil versus Butter in the Diet
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Ana Belén Segarra, Germán Domínguez-Vías, José Redondo, Magdalena Martínez-Cañamero, Manuel Ramírez-Sánchez, and Isabel Prieto
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virgin olive oil ,brain renin–angiotensin system ,fatty acid metabolism ,energy balance ,Nutrition. Foods and food supply ,TX341-641 - Abstract
The brain renin–angiotensin system (RAS) has been recently involved in the homeostatic regulation of energy. Our goal was to analyse the influence of a diet rich in saturated fatty acids (butter) against one enriched in monounsaturated fatty acids (olive oil) on hypothalamic RAS, and their relationship with the metabolism of fatty acids. Increases in body weight and visceral fat, together with an increase in aminopeptidase A expression and reductions in AngII and AngIV were observed in the hypothalamus of animals fed with the butter diet. In this group, a marked reduction in the expression of genes related to lipid metabolism (LPL, CD36, and CPT-1) was observed in liver and muscle. No changes were found in terms of body weight, total visceral fat and the expression of hepatic genes related to fatty acid metabolism in the olive oil diet. The expressions of LPL and CD36 were reduced in the muscles, although the decrease was lower than in the butter diet. At the same time, the fasting levels of leptin were reduced, no changes were observed in the hypothalamic expression of aminopeptidase A and decreases were noted in the levels of AngII, AngIV and AngIII. These results support that the type of dietary fat is able to modify the hypothalamic profile of RAS and the body energy balance, related to changes in lipid metabolism.
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- 2021
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16. Relationship of angiotensinase and vasopressinase enzymatic activities between hypothalamus and plasma in an obese rat model by high-fat diet
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Germán Domínguez-Vías, Ana Belén Segarra Robles, Manuel Ramírez Sánchez, and Sara Jiménez Serrano
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angiotensinases, vasopressinase, renin-angiotensin system, brain-blood connection, dietary fat ,Biology (General) ,QH301-705.5 - Abstract
High-fat diets are associated with the development of hypertension. However, a high intake of monounsaturated fat has been proposed to be a dietary factor that can decrease the incidence of hypertension. The renin-angiotensin system (RAS) and vasopressin interact to regulate blood pressure at central and peripheral level. In this study, we investigated the effect of different degrees of dietary fatty acid saturation in the control of RAS and vasopressin on brain-blood. To improve our understanding of their interaction and their relationship, we analyzed angiotensin- and vasopressin-metabolizing activities in hypothalamus and plasma, collected from Wistar rats fed during 24 weeks with diets enriched with extra virgin olive oil (monounsaturated fat) or butter plus cholesterol (saturated fat) compared with a standard diet. As results no angiotensinase and vasopressinase activities were found in hypothalamus and plasma, however significant correlations between enzymatic activities in both regions were noticed. They indicated that our results do not support the beneficial influence of extra virgin olive oil on central and systemic level to regulate blood pressure. Therefore, the substrates hydrolyzed by these activities as well as their functions may be similarly affected and suggest that these studies should be continued because of beneficial of Mediterranean diet, found previously in different works, which may also be an effective tool in the treatment of hypertension.
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- 2016
17. The Role of High Fat Diets and Liver Peptidase Activity in the Development of Obesity and Insulin Resistance in Wistar Rats
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Germán Domínguez-Vías, Ana Belén Segarra, Manuel Ramírez-Sánchez, and Isabel Prieto
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obesity ,high-fat diet ,olive oil ,aminopeptidase activity ,renin–angiotensin-system ,Nutrition. Foods and food supply ,TX341-641 - Abstract
High-fat diets (HFD) have been widely associated with an increased risk of metabolic disorders and overweight. However, a high intake of sources that are rich in monounsaturated fatty acids has been suggested as a dietary agent that is able to positively influence energy metabolism and vascular function. The main objective of this study was to analyze the role of dietary fats on hepatic peptidases activities and metabolic disorders. Three diets: standard (S), HFD supplemented with virgin olive oil (VOO), and HFD supplemented with butter plus cholesterol (Bch), were administered over six months to male Wistar rats. Plasma and liver samples were collected for clinical biochemistry and aminopeptidase activities (AP) analysis. The expression of inducible nitric oxide synthase (iNOS) was also determined by Western blot in liver samples. The diet supplement with VOO did not induce obesity, in contrast to the Bch group. Though the VOO diet increased the time that was needed to return to the basal levels of plasma glucose, the fasting insulin/glucose ratio and HOMA2-%B index (a homeostasis model index of insulin secretion and valuation of β-cell usefulness (% β-cell secretion)) were improved. An increase of hepatic membrane-bound dipeptidyl-peptidase 4 (DPP4) activity was found only in VOO rats, even if no differences in fasting plasma glucagon-like peptide 1 (GLP-1) were obtained. Both HFDs induced changes in hepatic pyroglutamyl-AP in the soluble fraction, but only the Bch diet increased the soluble tyrosyl-AP. Angiotensinase activities that are implicated in the metabolism of angiotensin II (AngII) to AngIV increased in the VOO diet, which was in agreement with the higher activity of insulin-regulated-AP (IRAP) in this group. Otherwise, the diet that was enriched with butter increased soluble gamma-glutamyl transferase (GGT) and Leucyl-AP, iNOS expression in the liver, and plasma NO. In summary, VOO increased the hepatic activity of AP that were related to glucose metabolism (DPP4, angiotensinases, and IRAP). However, the Bch diet increased activities that are implicated in the control of food intake (Tyrosine-AP), the index of hepatic damage (Leucine-AP and GGT), and the expression of hepatic iNOS and plasma NO. Taken together, these results support that the source of fat in the diet affects several peptidases activities in the liver, which could be related to alterations in feeding behavior and glucose metabolism.
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- 2020
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18. Membrane-derived phospholipids control synaptic neurotransmission and plasticity.
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Victoria García-Morales, Fernando Montero, David González-Forero, Guillermo Rodríguez-Bey, Laura Gómez-Pérez, María Jesús Medialdea-Wandossell, Germán Domínguez-Vías, José Manuel García-Verdugo, and Bernardo Moreno-López
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Biology (General) ,QH301-705.5 - Abstract
Synaptic communication is a dynamic process that is key to the regulation of neuronal excitability and information processing in the brain. To date, however, the molecular signals controlling synaptic dynamics have been poorly understood. Membrane-derived bioactive phospholipids are potential candidates to control short-term tuning of synaptic signaling, a plastic event essential for information processing at both the cellular and neuronal network levels in the brain. Here, we showed that phospholipids affect excitatory and inhibitory neurotransmission by different degrees, loci, and mechanisms of action. Signaling triggered by lysophosphatidic acid (LPA) evoked rapid and reversible depression of excitatory and inhibitory postsynaptic currents. At excitatory synapses, LPA-induced depression depended on LPA1/Gαi/o-protein/phospholipase C/myosin light chain kinase cascade at the presynaptic site. LPA increased myosin light chain phosphorylation, which is known to trigger actomyosin contraction, and reduced the number of synaptic vesicles docked to active zones in excitatory boutons. At inhibitory synapses, postsynaptic LPA signaling led to dephosphorylation, and internalization of the GABAAγ2 subunit through the LPA1/Gα12/13-protein/RhoA/Rho kinase/calcineurin pathway. However, LPA-induced depression of GABAergic transmission was correlated with an endocytosis-independent reduction of GABAA receptors, possibly by GABAAγ2 dephosphorylation and subsequent increased lateral diffusion. Furthermore, endogenous LPA signaling, mainly via LPA1, mediated activity-dependent inhibitory depression in a model of experimental synaptic plasticity. Finally, LPA signaling, most likely restraining the excitatory drive incoming to motoneurons, regulated performance of motor output commands, a basic brain processing task. We propose that lysophospholipids serve as potential local messengers that tune synaptic strength to precedent activity of the neuron.
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- 2015
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19. Influence of a Virgin Olive Oil versus Butter Plus Cholesterol-Enriched Diet on Testicular Enzymatic Activities in Adult Male Rats
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Germán Domínguez-Vías, Ana Belén Segarra, Magdalena Martínez-Cañamero, Manuel Ramírez-Sánchez, and Isabel Prieto
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testis-peptidase-activity ,renin-angiotensin-system ,high-fat-diet ,virgin-olive-oil ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
The aim of the present work was to improve our knowledge on the mechanisms underlying the beneficial or deleterious effects on testicular function of the so-called Mediterranean and Western diet by analyzing glutamyl aminopeptidase (GluAP), gamma glutamyl transpeptidase (GGT) and dipeptidyl peptidase IV (DPP IV) activities in testis, as enzymes involved in testicular function. Male Wistar rats (6 months old) were fed for 24 weeks with three different diets: standard (S), an S diet supplemented with virgin-olive-oil (20%) (VOO), or a S diet enriched with butter (20%) plus cholesterol (0.1%) (Bch). At the end of the experimental period, plasma lipid profiled (total triglycerides, total cholesterol and cholesterol fractions (HDL, LDL and VDL)) were measured. Enzymatic activities were determined by fluorimetric methods in soluble (sol) and membrane-bound (mb) fractions of testicular tissue using arylamide derivatives as substrates. Results indicated an increase in plasmatic triglycerides, total cholesterol, LDL and VLDL in Bch. A significant increase of mb GluAP and GGT activities was also found in this diet in comparison with the other two diets. Furthermore, significant and positive correlations were established between these activities and plasma triglycerides and/or total cholesterol. These results support a role for testicular GluAP and GGT activities in the effects of saturated fat (Western diet) on testicular functions. In contrast, VOO increased sol DPP IV activity in comparison with the other two diets, which support a role for this activity in the effects of monounsaturated fat (Mediterranean diet) on testicular function. The present results strongly support the influence of fatty acids and cholesterol on testicular GluAP and GGT activities and also provide support that the reported beneficial influence of the Mediterranean diet in male fertility may be mediated in part by an increase of testicular sol DPP IV activity.
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- 2017
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20. Physiological effects in a microgravity environment
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Manuel Ramírez-Sánchez, Germán Domínguez-Vías, and Isabel Prieto-Gomez
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Visual Arts and Performing Arts ,Event horizon ,Communication ,Medicine (miscellaneous) ,Environmental science ,Education ,Astrobiology - Published
- 2021
21. The Type of Fat in the Diet Influences Regulatory Aminopeptidases of the Renin-Angiotensin System and Stress in the Hypothalamic-Pituitary-Adrenal Axis in Adult Wistar Rats
- Author
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Manuel Ramírez-Sánchez, Germán Domínguez-Vías, Isabel Prieto, and Ana Belén Segarra
- Subjects
Male ,Pituitary-Adrenal System ,renin-angiotensin system ,Aminopeptidase ,Aminopeptidases ,chemistry.chemical_compound ,stress ,Adrenal Glands ,dipeptidyl peptidase IV ,TX341-641 ,Hypothalamuspituitary-adrenal axis ,Nutrition and Dietetics ,aminopeptidase ,Adrenal gland ,Fatty Acids ,hypothalamus-pituitary-adrenal axis ,medicine.anatomical_structure ,High-fat diet ,high-fat diet ,Hypothalamus ,Angiotensinases ,Hypothalamic–pituitary–adrenal axis ,Hypothalamo-Hypophyseal System ,medicine.medical_specialty ,angiotensinase ,Diet, High-Fat ,Stress ,Article ,Dipeptidyl peptidase ,Pituitary Gland, Anterior ,Stress, Physiological ,Internal medicine ,Endopeptidases ,Renin–angiotensin system ,medicine ,Animals ,Rats, Wistar ,Olive Oil ,Cholesterol ,Nutrition. Foods and food supply ,Feeding Behavior ,Metabolism ,Dietary Fats ,Rats ,Renin–angiotensin-system ,Endocrinology ,chemistry ,Dipeptidyl peptidase IV ,Food Science - Abstract
(1) Background: Prolonged feeding with a high-fat diet (HFD) acts as a stressor by activating the functions of the hypothalamic-pituitary-adrenal gland (HPA) stress axis, accompanied of hypertension by inducing the renin-angiotensin-aldosterone system. Angiotensinases enzymes are regulatory aminopeptidases of angiotensin metabolism, which together with the dipeptidyl peptidase IV (DPP-IV), pyroglutamyl- and tyrosyl-aminopeptidase (pGluAP, TyrAP), participate in cognitive, stress, metabolic and cardiovascular functions. These functions appear to be modulated by the type of fat used in the diet. (2) Methods: To analyze a possible coordinated response of aminopeptidases, their activities were simultaneously determined in the hypothalamus, adenohypophysis and adrenal gland of adult male rats fed diets enriched with monounsaturated (standard diet (S diet) supplemented with 20% virgin olive oil, VOO diet) or saturated fatty acids (diet S supplemented with 20% butter and 0.1% cholesterol, Bch diet). Aminopeptidase activities were measured by fluorimetry using 2-Naphthylamine as substrates. (3) Results: the hypothalamus did not show differences in any of the experimental diets. In the pituitary, the Bch diet stimulated the renin-angiotensin system (RAS) by increasing certain angiotensinase activities (alanyl-, arginyl- and cystinyl-aminopeptidase) with respect to the S and VOO diets. DPP-IV activity was increased with the Bch diet, and TyrAP activity decrease with the VOO diet, having both a crucial role on stress and eating behavior. In the adrenal gland, both HFDs showed an increase in angiotensinase aspartyl-aminopeptidase. The interrelation of angiotensinases activities in the tissues were depending on the type of diet. In addition, correlations were shown between angiotensinases and aminopeptidases that regulate stress and eating behavior. (4) Conclusions: Taken together, these results support that the source of fat in the diet affects several peptidases activities in the HPA axis, which could be related to alterations in RAS, stress and feeding behavior.
- Published
- 2021
22. Interaction between Angiotensinase Activities in Pituitary and Adrenal Glands of Wistar–Kyoto and Spontaneously Hypertensive Rats under Hypotensive or Hypertensive Treatments
- Author
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Germán Domínguez-Vías, Ana Belén Segarra, Marc de Gasparo, Isabel Prieto, Manuel Ramírez-Sánchez, Magdalena Martínez-Cañamero, Ana Belén Villarejo, and Inmaculada Banegas
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Male ,Pituitary gland ,Captopril ,Wistar–Kyoto ,030204 cardiovascular system & hematology ,Rats, Inbred WKY ,Aminopeptidases ,pituitary ,0302 clinical medicine ,Rats, Inbred SHR ,Adrenal Glands ,Enzyme Inhibitors ,Biology (General) ,Spectroscopy ,Chemistry ,adrenals ,General Medicine ,Propranolol ,Adrenals ,Computer Science Applications ,captopril ,Wistar kyoto ,NG-Nitroarginine Methyl Ester ,medicine.anatomical_structure ,Pituitary Gland ,Hypertension ,cardiovascular system ,Hypotension ,spontaneously hypertensive rats ,medicine.drug ,medicine.medical_specialty ,QH301-705.5 ,Gene Expression Regulation, Enzymologic ,Article ,Catalysis ,Inorganic Chemistry ,03 medical and health sciences ,L-NAME ,Internal medicine ,Endopeptidases ,Renin–angiotensin system ,medicine ,Animals ,cardiovascular diseases ,propranolol ,Physical and Theoretical Chemistry ,aminopeptidases ,QD1-999 ,Molecular Biology ,Antihypertensive Agents ,Organic Chemistry ,Wistar-Kyoto ,Metabolism ,Rats ,Endocrinology ,Blood pressure ,Pituitary ,Spontaneously hypertensive rats ,030217 neurology & neurosurgery - Abstract
This research was supported by the Ministry of Science and Innovation through project no. SAF 2008 04685 C02 01., In the present study, we analyzed the activity of several aminopeptidases (angiotensinases) involved in the metabolism of various angiotensin peptides, in pituitary and adrenal glands of untreated Wistar–Kyoto (WKY) and spontaneously hypertensive rats (SHR) or treated with the antihypertensive drugs captopril and propranolol or with the L-Arginine hypertensive analogue L-NG-Nitroarginine Methyl Ester (L-NAME). Intra- and inter-gland correlations between angiotensinase activities were also calculated. Membrane-bound alanyl-, cystinyl-, and glutamylaminopeptidase activities were determined fluorometrically using aminoacyl- -naphthylamide as substrates. Depending on the type of angiotensinase analyzed, the results reflect a complex picture showing substantial differences between glands, strains, and treatments. Alanyl-aminopeptidase responsible for the metabolism of Ang III to Ang IV appears to be the most active angiotensinase in both pituitary and adrenals of WKY and particularly in SHR. Independently of treatment, most positive correlations are observed in the pituitary gland of WKY whereas such positive correlations are predominant in adrenals of SHR. Negative inter-gland correlations were observed in control SHR and L-NAME treated WKY. Positive inter-gland correlations were observed in captopril-treated SHR and propranolol-treated WKY. These results may reflect additional mechanisms for increasing or decreasing systolic blood pressure in WKY or SHR., Spanish Government SAF 2008 04685 C02 01
- Published
- 2021
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23. Hypothalamic Renin–Angiotensin System and Lipid Metabolism: Effects of Virgin Olive Oil versus Butter in the Diet
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Magdalena Martínez-Cañamero, José Redondo, Ana Belén Segarra, Isabel Prieto, Manuel Ramírez-Sánchez, and Germán Domínguez-Vías
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CD36 Antigens ,Leptin ,Male ,brain renin–angiotensin system ,CD36 ,Gene Expression ,030204 cardiovascular system & hematology ,Weight Gain ,Renin-Angiotensin System ,chemistry.chemical_compound ,Mice ,0302 clinical medicine ,Virgin olive oil ,Brain renin–angiotensin system ,Mice, Inbred ICR ,Nutrition and Dietetics ,biology ,Chemistry ,Angiotensin II ,Fasting ,Angiotensin III ,Liver ,virgin olive oil ,fatty acid metabolism ,Hypothalamus ,lcsh:Nutrition. Foods and food supply ,medicine.medical_specialty ,lcsh:TX341-641 ,030209 endocrinology & metabolism ,Energy balance ,Intra-Abdominal Fat ,Diet, High-Fat ,Glutamyl Aminopeptidase ,Real-Time Polymerase Chain Reaction ,Article ,03 medical and health sciences ,Internal medicine ,Renin–angiotensin system ,medicine ,Animals ,RNA, Messenger ,Muscle, Skeletal ,Olive Oil ,Fatty acid metabolism ,Body Weight ,Lipid metabolism ,Metabolism ,Lipid Metabolism ,energy balance ,Lipoprotein Lipase ,Endocrinology ,biology.protein ,Butter ,Energy Metabolism ,Homeostasis ,Food Science - Abstract
The brain renin–angiotensin system (RAS) has been recently involved in the homeostatic regulation of energy. Our goal was to analyse the influence of a diet rich in saturated fatty acids (butter) against one enriched in monounsaturated fatty acids (olive oil) on hypothalamic RAS, and their relationship with the metabolism of fatty acids. Increases in body weight and visceral fat, together with an increase in aminopeptidase A expression and reductions in AngII and AngIV were observed in the hypothalamus of animals fed with the butter diet. In this group, a marked reduction in the expression of genes related to lipid metabolism (LPL, CD36, and CPT-1) was observed in liver and muscle. No changes were found in terms of body weight, total visceral fat and the expression of hepatic genes related to fatty acid metabolism in the olive oil diet. The expressions of LPL and CD36 were reduced in the muscles, although the decrease was lower than in the butter diet. At the same time, the fasting levels of leptin were reduced, no changes were observed in the hypothalamic expression of aminopeptidase A and decreases were noted in the levels of AngII, AngIV and AngIII. These results support that the type of dietary fat is able to modify the hypothalamic profile of RAS and the body energy balance, related to changes in lipid metabolism., University of Jaen PP2009/13/03
- Published
- 2021
24. Olive oil and male fertility
- Author
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Germán Domínguez-Vías, Manuel Ramírez-Sánchez, Isabel Prieto, and Ana Belén Segarra
- Subjects
Infertility ,Antioxidant ,medicine.diagnostic_test ,Mediterranean diet ,Cholesterol ,medicine.medical_treatment ,Context (language use) ,Biology ,medicine.disease ,Sperm ,Lipid peroxidation ,chemistry.chemical_compound ,chemistry ,medicine ,Food science ,Lipid profile - Abstract
Male infertility has demonstrated to be a global health problem during last years. In this context, environmental contaminants and lifestyle mainly diet play an important role at the same time that provides an opportunity to develop new prevention strategies. It is well stablished that diet rich in raw vegetables and fruit, similar to Mediterranean diet, could play a beneficial effect on spermatogenesis and reproductive function related to a high intake of antioxidants. In fact, the main cause of infertility in men is due to direct damage of reactive oxygen species at the nucleus and mitochondria DNA, and the lipid peroxidation in the membrane of the sperm. On the other hand, Western diet has demonstrated to exert a negative impact on male fertility, as it is usually rich in saturated fatty acids and cholesterol. The changes in plasmatic lipid profile and the increase of cholesterol correlate with less sperm functionality. Virgin olive oil, the major lipid source in the Mediterranean diet, provide a high amount of antioxidant, mainly polyphenols and others minors components, together a beneficial lipid composition, characterized by the contribution of monounsaturated fatty acids. Besides that, compared with others dietary fats, virgin olive oil presents a particular effect on several peptidases activities in testis, and these results seem to be related to changes in plasma lipid profile. Changes in angiotensinase activities in testis are able to modulate local renin–angiotensin system, with relevant functions in male fertility.
- Published
- 2021
25. Asymmetrical influence of a standard light/dark cycle and constant light conditions on the alanyl-aminopeptidase activity of the left and right retinas in adult male rats
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M. Ramírez-Sánchez, Germán Domínguez-Vías, Juan de Dios Luna, Magdalena Martínez-Cañamero, G. Aretxaga, Isabel Prieto, and Ana Belén Segarra
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0301 basic medicine ,Male ,medicine.medical_specialty ,Period (gene) ,media_common.quotation_subject ,Photoperiod ,Neuropeptide ,CD13 Antigens ,Retina ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,chemistry.chemical_compound ,0302 clinical medicine ,Internal medicine ,medicine ,Brain asymmetry ,Contrast (vision) ,Animals ,media_common ,Suprachiasmatic nucleus ,Retinal ,Reference Standards ,Sensory Systems ,Circadian Rhythm ,Rats ,Ophthalmology ,030104 developmental biology ,Endocrinology ,medicine.anatomical_structure ,chemistry ,Peripheral nervous system ,Models, Animal ,030221 ophthalmology & optometry ,sense organs ,Photic Stimulation - Abstract
The retina acts as an independent clock informing the central pacemaker, the suprachiasmatic nucleus, under environmental light conditions, with consequences of such inputs for the central and peripheral nervous system. Differences in the behavior of the left and right retinas depending on environmental light conditions may influence the information projected to the brain hemispheres. The retina possesses neuropeptides that act as neurotransmitters or neuromodulators. Alanyl-aminopeptidase (AlaAP, EC 3.4.11.2) activity regulates some of these neuropeptides and therefore reflects their function. We analyzed AlaAP activity in the left and right retinas of adult male rats at successive time points under standard (12/12 h light/dark cycle) and nonstandard (constant light) conditions. AlaAP activity was measured fluorometrically using alanyl-beta-naphthylamide as the substrate. Under standard conditions, there were no differences in the left or right retina between time points, with the left retina predominating, particularly in the light period. In contrast, under constant light, no left versus right differences were observed, but significant differences between time points appeared. In comparison with standard conditions, constant conditions led to significantly higher AlaAP activity. Considering all the left retina data in comparison with all the right retina data, no correlation was found between the left and right retinas under standard conditions, but a significant positive correlation was observed under constant light. These results demonstrate an asymmetrical response of retinal AlaAP activity to changes in environmental light conditions, which may affect the functions in which the substrates of AlaAP are involved and the information projected to the brain hemispheres.
- Published
- 2020
26. The Role of High Fat Diets and Liver Peptidase Activity in the Development of Obesity and Insulin Resistance in Wistar Rats
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Manuel Ramírez-Sánchez, Germán Domínguez-Vías, Ana Belén Segarra, and Isabel Prieto
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Male ,0301 basic medicine ,obesity ,Nitric Oxide Synthase Type II ,Aminopeptidase activity ,chemistry.chemical_compound ,0302 clinical medicine ,Glucagon-Like Peptide 1 ,Nutrition and Dietetics ,biology ,gamma-Glutamyltransferase ,olive oil ,Nitric oxide synthase ,high-fat diet ,High-fat diet ,Liver ,lcsh:Nutrition. Foods and food supply ,medicine.medical_specialty ,Dipeptidyl Peptidase 4 ,Pyroglutamyl-Peptidase I ,lcsh:TX341-641 ,030209 endocrinology & metabolism ,Carbohydrate metabolism ,Diet, High-Fat ,Nitric Oxide ,Article ,03 medical and health sciences ,Insulin resistance ,Internal medicine ,medicine ,Animals ,Obesity ,Rats, Wistar ,renin–angiotensin-system ,Cholesterol ,aminopeptidase activity ,Feeding Behavior ,Metabolism ,Glucose Tolerance Test ,medicine.disease ,Angiotensin II ,Renin–angiotensin-system ,030104 developmental biology ,Endocrinology ,chemistry ,Basal (medicine) ,biology.protein ,Insulin Resistance ,Energy Intake ,Homeostasis ,Olive oil ,Peptide Hydrolases ,Food Science - Abstract
Technical and human support provided by CICT and CEPA of Universidad de Jaén (UJA, MINECO, Junta de Andalucía; FEDER) is gratefully acknowledged., High-fat diets (HFD) have been widely associated with an increased risk of metabolic disorders and overweight. However, a high intake of sources that are rich in monounsaturated fatty acids has been suggested as a dietary agent that is able to positively influence energy metabolism and vascular function. The main objective of this study was to analyze the role of dietary fats on hepatic peptidases activities and metabolic disorders. Three diets: standard (S), HFD supplemented with virgin olive oil (VOO), and HFD supplemented with butter plus cholesterol (Bch), were administered over six months to male Wistar rats. Plasma and liver samples were collected for clinical biochemistry and aminopeptidase activities (AP) analysis. The expression of inducible nitric oxide synthase (iNOS) was also determined by Western blot in liver samples. The diet supplement with VOO did not induce obesity, in contrast to the Bch group. Though the VOO diet increased the time that was needed to return to the basal levels of plasma glucose, the fasting insulin/glucose ratio and HOMA2-%B index (a homeostasis model index of insulin secretion and valuation of β-cell usefulness (% β-cell secretion)) were improved. An increase of hepatic membrane-bound dipeptidyl-peptidase 4 (DPP4) activity was found only in VOO rats, even if no differences in fasting plasma glucagon-like peptide 1 (GLP-1) were obtained. Both HFDs induced changes in hepatic pyroglutamyl-AP in the soluble fraction, but only the Bch diet increased the soluble tyrosyl-AP. Angiotensinase activities that are implicated in the metabolism of angiotensin II (AngII) to AngIV increased in the VOO diet, which was in agreement with the higher activity of insulin-regulated-AP (IRAP) in this group. Otherwise, the diet that was enriched with butter increased soluble gamma-glutamyl transferase (GGT) and Leucyl-AP, iNOS expression in the liver, and plasma NO. In summary, VOO increased the hepatic activity of AP that were related to glucose metabolism (DPP4, angiotensinases, and IRAP). However, the Bch diet increased activities that are implicated in the control of food intake (Tyrosine-AP), the index of hepatic damage (Leucine-AP and GGT), and the expression of hepatic iNOS and plasma NO. Taken together, these results support that the source of fat in the diet affects several peptidases activities in the liver, which could be related to alterations in feeding behavior and glucose metabolism., This work was supported by grant code: ACCIÓN 1 PAIUJA 2019 2020: BIO221.
- Published
- 2020
27. Effects of Virgin Olive Oil on Blood Pressure and Renal Aminopeptidase Activities in Male Wistar Rats
- Author
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Manuel Ramírez-Sánchez, Ana Belén Segarra, Germán Domínguez-Vías, and Isabel Prieto
- Subjects
Male ,systolic blood pressure ,Sympathetic nervous system ,Mediterranean diet ,Saturated fat ,Blood Pressure ,030204 cardiovascular system & hematology ,Diet, Mediterranean ,Aminopeptidases ,Renin-Angiotensin System ,chemistry.chemical_compound ,0302 clinical medicine ,Biology (General) ,Spectroscopy ,Kidney Medulla ,Kidney ,Chemistry ,General Medicine ,Computer Science Applications ,Cholesterol ,high-fat diet ,medicine.anatomical_structure ,virgin olive oil ,Hypertension ,medicine.medical_specialty ,Kidney Cortex ,QH301-705.5 ,Renal cortex ,030209 endocrinology & metabolism ,Article ,Catalysis ,Inorganic Chemistry ,03 medical and health sciences ,Internal medicine ,Renin–angiotensin system ,medicine ,Renal medulla ,Animals ,Obesity ,Rats, Wistar ,Physical and Theoretical Chemistry ,Olive Oil ,QD1-999 ,Molecular Biology ,Organic Chemistry ,renal–aminopeptidase activities ,Dietary Fats ,Rats ,Endocrinology ,Butter - Abstract
High saturated fat diets have been associated with the development of obesity and hypertension, along with other pathologies related to the metabolic syndrome. In contrast, the Mediterranean diet, characterized by its high content of monounsaturated fatty acids, has been proposed as a dietary factor capable of positively regulating cardiovascular function. These effects have been linked to changes in the local renal renin angiotensin system (RAS) and the activity of the sympathetic nervous system. The main goal of this study was to analyze the role of two dietary fat sources on aminopeptidases activities involved in local kidney RAS. Male Wistar rats (six months old) were fed during 24 weeks with three different diets: the standard diet (S), the standard diet supplemented with virgin olive oil (20%) (VOO), or the standard diet enriched with butter (20%) plus cholesterol (0.1%) (Bch). Kidney samples were separated in medulla and cortex for aminopeptidase activities (AP) assay. Urine samples were collected for routine analysis by chemical tests. Aminopeptidase activities were determined by fluorometric methods in soluble (sol) and membrane-bound (mb) fractions of renal tissue, using arylamide derivatives as substrates. After the experimental period, the systolic blood pressure (SBP) values were similar in standard and VOO animals, and significantly lower than in the Bch group. At the same time, a significant increase in GluAP and IRAP activities were found in renal medulla of Bch animals. However, in VOO group the increase of GluAP activity in renal medulla was lower, while AspAP activity decreased in the renal cortex. Furthermore, the VOO diet also affected other aminopeptidase activities, such as TyrAP and pGluAP, related to the regulation of the sympathetic nervous system and the metabolic rate. These results support the beneficial effect of VOO in the regulation of SBP through changes in local AP activities of the kidney.
- Published
- 2021
28. Diurnal opposite variation between angiotensinase activities in photo–neuro–endocrine tissues of rats
- Author
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Germán Domínguez-Vías, Isabel Prieto, Manuel Ramírez-Sánchez, Juan de Dios Luna, Garbine Aretxaga-Maza, and Marc de Gasparo
- Subjects
Male ,0301 basic medicine ,medicine.medical_specialty ,Light ,genetic structures ,Physiology ,Period (gene) ,Hypothalamus ,Glutamyl Aminopeptidase ,Renin-Angiotensin System ,03 medical and health sciences ,0302 clinical medicine ,Physiology (medical) ,Internal medicine ,Endopeptidases ,Renin–angiotensin system ,medicine ,Animals ,Endocrine system ,Circadian rhythm ,Rats, Wistar ,Retina ,Chemistry ,Metabolism ,Circadian Rhythm ,030104 developmental biology ,Endocrinology ,medicine.anatomical_structure ,Pituitary Gland ,Hypertension ,Darkness ,sense organs ,030217 neurology & neurosurgery - Abstract
Central and peripheral renin-angiotensin systems (RASs) act in a coordinated manner for the physiologic functions regulated by neuroendocrine events. However, whereas the diurnal rhythm of peripheral circulatory and tissue RASs is well known, the circadian behaviour of their components in central photo-neuro-endocrine structures, key elements for the control of circadian rhythms, has been barely studied. In the present study, we analysed the aspartyl- (AspAP) and glutamyl-aminopeptidase (GluAP) (aminopeptidase A) activities, the angiotensinases responsible for the metabolism of Ang I to Ang 2-10 and Ang II to Ang III, respectively, in the retina, anterior hypothalamus and pituitary at different light and dark time-points of a 12:12 h light:dark cycle (7-19 h light), using arylamide derivatives as substrates. The results demonstrated that while retina and pituitary exhibited their highest levels of AspAP activity in the light period and the lowest in the dark one, the contrary occurred in the hypothalamus - the lowest levels were observed in light conditions and the highest in darkness. The outcome for GluAP showed the highest levels in the light period and the lowest in the dark one in the three tissues analysed. In conclusion, changes in angiotensinase activities throughout the daytime may cause changes of their respective substrates and derived peptides and, consequently, in their functions. This observation may have implications for the treatment of hypertension.
- Published
- 2017
29. Sp1-regulated expression of p11 contributes to motor neuron degeneration by membrane insertion of TASK1
- Author
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Federico Portillo, Antonio Campos-Caro, Rosa M. Soler, Germán Domínguez-Vías, Noura Issaoui, Laura Gómez-Pérez, David González-Forero, Bernardo Moreno-López, Ángela Gento-Caro, Guillermo Rodríguez-Bey, Victoria García-Morales, Ana Garcera, and Bioquímica y Biología Molecular, Microbiología, Medicina Preventiva, Salud Pública
- Subjects
Male ,0301 basic medicine ,General Physics and Astronomy ,02 engineering and technology ,Degeneration (medical) ,Ion channels in the nervous system ,Membrane Potentials ,Mice ,Amyotrophic lateral sclerosis ,lcsh:Science ,Promoter Regions, Genetic ,Annexin A2 ,Motor Neurons ,Membrane potential ,Regulation of gene expression ,Multidisciplinary ,S100 Proteins ,Neurodegeneration ,Signal transducing adaptor protein ,021001 nanoscience & nanotechnology ,Spinal Cord ,Gene Knockdown Techniques ,Female ,0210 nano-technology ,congenital, hereditary, and neonatal diseases and abnormalities ,Sp1 Transcription Factor ,Science ,Primary Cell Culture ,Mice, Transgenic ,Nerve Tissue Proteins ,Biology ,Neuroprotection ,Article ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,Potassium Channels, Tandem Pore Domain ,medicine ,Animals ,Humans ,Sp1 transcription factor ,Amyotrophic Lateral Sclerosis ,Cell Membrane ,General Chemistry ,medicine.disease ,Rats ,Disease Models, Animal ,HEK293 Cells ,030104 developmental biology ,Gene Expression Regulation ,Nerve Degeneration ,lcsh:Q ,Neuroscience - Abstract
Disruption in membrane excitability contributes to malfunction and differential vulnerability of specific neuronal subpopulations in a number of neurological diseases. The adaptor protein p11, and background potassium channel TASK1, have overlapping distributions in the CNS. Here, we report that the transcription factor Sp1 controls p11 expression, which impacts on excitability by hampering functional expression of TASK1. In the SOD1-G93A mouse model of ALS, Sp1-p11-TASK1 dysregulation contributes to increased excitability and vulnerability of motor neurons. Interference with either Sp1 or p11 is neuroprotective, delaying neuron loss and prolonging lifespan in this model. Nitrosative stress, a potential factor in human neurodegeneration, stimulated Sp1 expression and human p11 promoter activity, at least in part, through a Sp1-binding site. Disruption of Sp1 or p11 also has neuroprotective effects in a traumatic model of motor neuron degeneration. Together our work suggests the Sp1-p11-TASK1 pathway is a potential target for treatment of degeneration of motor neurons., The adaptor protein p11 and K+ channel TASK1 have overlapping distributions in the CNS. Here, the authors demonstrate that the transcription factor Sp1 regulates p11 levels, which in turn affects intrinsic membrane properties and can contribute to degeneration of motor neurons in disease and injury models.
- Published
- 2019
30. Cinema Seminar as a guidance resource in the election of undergraduate dissertation in the subject of physiology
- Author
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Germán DOMÍNGUEZ VÍAS, Borja MARÍN AMIEVA, and Elena LÓPEZ MARTÍN
- Subjects
undergraduate dissertation ,lcsh:R5-920 ,medicine ,orientación ,cine ,physiology ,trabajo fin de grado ,cinema ,lcsh:Medicine (General) ,fisiología ,medicina ,orientation - Abstract
Physiology, in the medical and other health sciences or experimental degrees, is one of the subjects with morevariety of themes that a student can choose for the development of his undergraduate dissertation. The complexityof the syllabus, together with the disorientation to the lack of ideas, incapacitates the students to choose theirproject. As a main objective, the development of a seminar using the Cinema as an auxiliary tool would help to guidein the choice of an initial idea of the whole physiology syllabus. The review of each theme, or specific thematic block, would be linked to the visualization of short film fragments (30 seconds ? 3 minutes) that would reflect a crucial moment of different physiological states of an individual. The transition of topics should be paused to opt to comment or reflect on aspects and ideas. A template with different options per unit helps to mark the most valued aspects. From the conclusions obtained, a final summary of the assimilated allows to obtain a previous idea of a possible chosen theme. We can assure that the Cinema offers the students a useful experience for the resolution ofconflicts after acquiring knowledge, thinking skills, attitudes and values.
- Published
- 2018
31. The Disaster of 96: An educational way of explaining the physiological reactions produced as a consequence of exposure to low oxygen pressure at high altitude using the film Everest (2015)
- Author
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Germán DOMÍNGUEZ VÍAS
- Subjects
edema pulmonar ,Altitude, Barometric pressure, Alveolar oxygen pressure, Hypoxia, Pulmonary edema, Cerebral edema ,lcsh:R5-920 ,hipoxia ,presión de oxigeno alveolar ,altitud ,edema cerebral ,presión barométrica ,lcsh:Medicine (General) - Abstract
The 96 Mount Everest Disaster refers to the events that took place from May 10 to 11, 1996, when eight people caught in a storm were died, some during the ascent and, those who had already reached the Summit, while they descended. The film Everest (2015) faithfully reflects the previous symptoms that occurred during ascension, an important reason to understand the effects of altitude and low gas pressures on the human body. In this paper we address both problems, Everest can help students to understand and reflect on the challenges for body homeostasis that take place at great heights.
- Published
- 2018
32. Influence of a Virgin Olive Oil versus Butter Plus Cholesterol-Enriched Diet on Testicular Enzymatic Activities in Adult Male Rats
- Author
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Isabel Prieto, Germán Domínguez-Vías, Manuel Ramírez-Sánchez, Magdalena Martínez-Cañamero, and Ana Belén Segarra
- Subjects
Male ,0301 basic medicine ,Very low-density lipoprotein ,Mediterranean diet ,Saturated fat ,lcsh:Chemistry ,chemistry.chemical_compound ,0302 clinical medicine ,Testis ,Gamma-glutamyltransferase ,lcsh:QH301-705.5 ,Spectroscopy ,testis-peptidase-activity ,renin-angiotensin-system ,high-fat-diet ,virgin-olive-oil ,gamma-Glutamyltransferase ,General Medicine ,Computer Science Applications ,Cholesterol ,medicine.medical_specialty ,Dipeptidyl Peptidase 4 ,030209 endocrinology & metabolism ,Biology ,Glutamyl Aminopeptidase ,Article ,Catalysis ,Dipeptidyl peptidase ,Inorganic Chemistry ,03 medical and health sciences ,Dietary Fats, Unsaturated ,Internal medicine ,medicine ,Animals ,Rats, Wistar ,Physical and Theoretical Chemistry ,Olive Oil ,Molecular Biology ,Dipeptidyl peptidase-4 ,Body Weight ,Organic Chemistry ,030104 developmental biology ,Endocrinology ,Solubility ,chemistry ,lcsh:Biology (General) ,lcsh:QD1-999 ,Glutamyl aminopeptidase ,Butter ,biology.protein - Abstract
The aim of the present work was to improve our knowledge on the mechanisms underlying the beneficial or deleterious effects on testicular function of the so-called Mediterranean and Western diet by analyzing glutamyl aminopeptidase (GluAP), gamma glutamyl transpeptidase (GGT) and dipeptidyl peptidase IV (DPP IV) activities in testis, as enzymes involved in testicular function. Male Wistar rats (6 months old) were fed for 24 weeks with three different diets: standard (S), an S diet supplemented with virgin-olive-oil (20%) (VOO), or a S diet enriched with butter (20%) plus cholesterol (0.1%) (Bch). At the end of the experimental period, plasma lipid profiled (total triglycerides, total cholesterol and cholesterol fractions (HDL, LDL and VDL)) were measured. Enzymatic activities were determined by fluorimetric methods in soluble (sol) and membrane-bound (mb) fractions of testicular tissue using arylamide derivatives as substrates. Results indicated an increase in plasmatic triglycerides, total cholesterol, LDL and VLDL in Bch. A significant increase of mb GluAP and GGT activities was also found in this diet in comparison with the other two diets. Furthermore, significant and positive correlations were established between these activities and plasma triglycerides and/or total cholesterol. These results support a role for testicular GluAP and GGT activities in the effects of saturated fat (Western diet) on testicular functions. In contrast, VOO increased sol DPP IV activity in comparison with the other two diets, which support a role for this activity in the effects of monounsaturated fat (Mediterranean diet) on testicular function. The present results strongly support the influence of fatty acids and cholesterol on testicular GluAP and GGT activities and also provide support that the reported beneficial influence of the Mediterranean diet in male fertility may be mediated in part by an increase of testicular sol DPP IV activity.
- Published
- 2017
33. Membrane-Derived Phospholipids Control Synaptic Neurotransmission and Plasticity
- Author
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Fernando Montero, Laura Gómez-Pérez, Germán Domínguez-Vías, María Jesús Medialdea-Wandossell, David González-Forero, Guillermo Rodríguez-Bey, José Manuel García-Verdugo, Bernardo Moreno-López, and Victoria García-Morales
- Subjects
Male ,Patch-Clamp Techniques ,QH301-705.5 ,Neurotransmission ,Biology ,Inhibitory postsynaptic potential ,Synaptic Transmission ,General Biochemistry, Genetics and Molecular Biology ,Mice ,Pregnancy ,Synaptic augmentation ,Metaplasticity ,Animals ,Rats, Wistar ,Biology (General) ,Motor Neurons ,rho-Associated Kinases ,Neuronal Plasticity ,General Immunology and Microbiology ,Calcineurin ,General Neuroscience ,Receptors, GABA-A ,Cell biology ,Synaptic fatigue ,Biochemistry ,Synapses ,Synaptic plasticity ,Excitatory postsynaptic potential ,Female ,lipids (amino acids, peptides, and proteins) ,Synaptic signaling ,Lysophospholipids ,rhoA GTP-Binding Protein ,General Agricultural and Biological Sciences ,Research Article - Abstract
Synaptic communication is a dynamic process that is key to the regulation of neuronal excitability and information processing in the brain. To date, however, the molecular signals controlling synaptic dynamics have been poorly understood. Membrane-derived bioactive phospholipids are potential candidates to control short-term tuning of synaptic signaling, a plastic event essential for information processing at both the cellular and neuronal network levels in the brain. Here, we showed that phospholipids affect excitatory and inhibitory neurotransmission by different degrees, loci, and mechanisms of action. Signaling triggered by lysophosphatidic acid (LPA) evoked rapid and reversible depression of excitatory and inhibitory postsynaptic currents. At excitatory synapses, LPA-induced depression depended on LPA1/Gαi/o-protein/phospholipase C/myosin light chain kinase cascade at the presynaptic site. LPA increased myosin light chain phosphorylation, which is known to trigger actomyosin contraction, and reduced the number of synaptic vesicles docked to active zones in excitatory boutons. At inhibitory synapses, postsynaptic LPA signaling led to dephosphorylation, and internalization of the GABAAγ2 subunit through the LPA1/Gα12/13-protein/RhoA/Rho kinase/calcineurin pathway. However, LPA-induced depression of GABAergic transmission was correlated with an endocytosis-independent reduction of GABAA receptors, possibly by GABAAγ2 dephosphorylation and subsequent increased lateral diffusion. Furthermore, endogenous LPA signaling, mainly via LPA1, mediated activity-dependent inhibitory depression in a model of experimental synaptic plasticity. Finally, LPA signaling, most likely restraining the excitatory drive incoming to motoneurons, regulated performance of motor output commands, a basic brain processing task. We propose that lysophospholipids serve as potential local messengers that tune synaptic strength to precedent activity of the neuron., Lysophospholipids derived from membranes are important regulators of neurotransmission, acting as local messengers that couple synaptic strength to recent neuronal activity., Author Summary Neuronal networks are modules of synaptic connectivity that underlie all brain functions, from simple reflexes to complex cognitive processes. Synaptic plasticity allows these networks to adapt to changing external and internal environments. Membrane-derived bioactive phospholipids are potential candidates to control short-term synaptic plasticity. We demonstrate that lysophosphatidic acid (LPA), an important intermediary in lipid metabolism, depresses the main excitatory and inhibitory synaptic systems by different mechanisms. LPA depresses inhibitory synaptic transmission by reducing the number of postsynaptic receptors at inhibitory synapses; whereas it depresses excitatory synaptic transmission by decreasing the size of the ready-to-use synaptic vesicle pool at excitatory terminals. Finally, we demonstrate that LPA signaling contributes to the performance of motor output commands in adult animals. Our data documents that synaptic strength and neuronal activity are modulated by products of membrane phospholipid metabolism, which suggests that bioactive phospholipids are candidates in coupling brain function to the metabolic status of the organism.
- Published
- 2015
34. Poster abstracts
- Author
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Germán Domínguez-Vías
- Subjects
Nutrition and Dietetics ,Endocrinology, Diabetes and Metabolism ,Medicine (miscellaneous) - Published
- 2010
35. Seminario de Cine como recurso orientativo en la elección de Trabajo Fin de Grado en la asignatura de Fisiología
- Author
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Germán DOMÍNGUEZ VÍAS, Borja MARÍN AMIEVA, and Elena LÓPEZ MARTÍN
- Subjects
trabajo fin de grado ,fisiología ,cine ,medicina ,orientación. ,Medicine (General) ,R5-920 - Abstract
Fisiología, en los grados de Medicina y otras ciencias de la salud o experimental, es una de las asignaturas con másvariedad de temas que puede optar un alumno para el desarrollo de su trabajo de fin de grado. La complejidad deltemario, junto con la desorientación ante la falta de ideas, incapacita al alumnado para la elección de su proyecto.Como objetivo principal, el desarrollo de un seminario empleando el Cine como herramienta auxiliar ayudaría aorientar en la elección de una idea inicial de entre todo el temario de fisiología. El repaso de cada tema, o bloquetemático específico, estaría vinculado a la visualización de fragmentos cortos de películas (30 segundos ? 3 minutos)que reflejarían un momento crucial de diferentes estados fisiológicos de un individuo. La transición de temas debeser pausada para optar a comentar o reflexionar sobre aspectos e ideas. Una plantilla con distintas opciones por unidad ayuda a marcar los aspectos más valorados. De las conclusiones obtenidas, un resumen final de lo asimiladopermite obtener una idea previa de un posible tema electo. Podemos asegurar que el Cine brinda al alumnado unaexperiencia útil para la resolución de conflictos tras la adquisición de conocimientos, habilidades de reflexión, actitudesy valores.
- Published
- 2018
36. El Desastre del 96: Una forma educativa de explicar las reacciones fisiológicas producidas como consecuencia de la exposición a la baja presión de oxígeno a gran altitud usando la película Everest (2015)
- Author
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Germán DOMÍNGUEZ VÍAS
- Subjects
altitud, presión barométrica, presión de oxigeno alveolar, hipoxia, edema pulmonar, edema cerebral ,Medicine (General) ,R5-920 - Abstract
El Desastre del 96 del Monte Everest se refiere a los eventos ocurrido del 10 al 11 de mayo de 1996, cuando ocho personas atrapadas en un temporal perdieron la vida, algunos durante el ascenso y, aquellos que ya habían hecho cumbre, mientras descendían. La película Everest (2015) refleja fielmente los síntomas previos ocurridos durante la ascensión, razón importante para comprender los efectos de la altura y de las bajas presiones de gases sobre el cuerpo humano. En este trabajo se aborda ambos problemas, Everest puede ayudar al alumnado a entender y reflexionar sobre los desafíos para la homeostasis corporal que tienen lugar a grandes alturas.
- Published
- 2018
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