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3 results on '"metabolism, Male, Mice, Mice"'

1. Increased expression of adenosine triphosphate-sensitive K+ channels in mitral dysfunction: mechanically stimulated transcription and hypoxia-induced protein stability?

Author

Raeis Dauvé, V., Philip Couderc, P., Faggian, Giuseppe, Tessari, Maddalena, Roatti, A., Milano, Aldo Domenico, Bochaton Piallat, M., and Baertschi, A. J.

Subjects
Male, Potassium Channels, Myocardium/metabolism, Messenger, Blood Pressure, Messenger/metabolism, ddc:616.07, Mice, Anoxia, KATP Channels, Anoxia/metabolism, Hypoxia, Kir6.2 expression, Alpha Subunit/metabolism, Mice, Knockout, Mitral Valve Insufficiency/metabolism, Protein Stability, Mitral Valve Insufficiency, Heart Ventricles/metabolism, Middle Aged, Inwardly Rectifying, KATP Channels/metabolism, Aged, Animals, Anoxia, metabolism, Blood Gas Analysis, Blood Pressure, Echocardiography, Female, Gene Expression Regulation, Heart Ventricles, metabolism, Humans, Hypoxia-Inducible Factor 1, alpha Subunit, metabolism, KATP Channels, metabolism, Male, Mice, Mice, Knockout, Middle Aged, Mitral Valve Insufficiency, metabolism, Myocardium, metabolism, Oxygen, physiology, Partial Pressure, Potassium Channels, metabolism, Protein Stability, RNA, metabolism, Stress, Mechanical, Echocardiography, cardiovascular system, Female, Hypoxia-Inducible Factor 1, transcription, endocrine system, Heart Ventricles, Knockout, Partial Pressure, Oxygen/physiology, ischemia, Stress, Inwardly Rectifying/metabolism, Animals, Humans, RNA, Messenger, Potassium Channels, Inwardly Rectifying, Aged, Myocardium, mechanical stress, Hypoxia-Inducible Factor 1, alpha Subunit, ddc:616.8, Oxygen, Gene Expression Regulation, physiology, RNA, Stress, Mechanical, mitral regurgitation, ddc:618.92, Blood Gas Analysis, metabolism
Abstract

OBJECTIVES The aim of this study was to test whether adenosine triphosphate sensitive K(+) (KATP) channel expression relates to mechanical and hypoxic stress within the left human heart. BACKGROUND The KATP channels play a vital role in preserving the metabolic integrity of the stressed heart. However the mechanisms that govern the expression of their subunits (e.g. potassium inward rectifier [Kir] 6.2) in adult pathologies are mostly unknown. METHODS We collected biopsies from the 4 cardiac chambers and 50 clinical parameters from 30 surgical patients with severe mitral dysfunction. Proteins and messenger ribonucleic acids (mRNAs) of KATP pore subunits and mRNAs of their known transcriptional regulators (forkhead box [FOX] F2 FOXO1 FOXO3 and hypoxia inducible factor [HIF] 1a) were measured respectively by Western blotting immunohistochemistry and quantitative real time polymerase chain reaction and submitted to statistical analysis. RESULTS In all heart chambers Kir6.2 mRNA correlated with HIF 1a mRNA. Neither Kir6.1 nor Kir6.2 proteins positively correlated with their respective mRNAs. The HIF 1a mRNA related in the left ventricle to aortic pressure in the left atrium to left atrial pressure and in all heart chambers to a decreased Kir6.2 protein/mRNA ratio. Interestingly in the left heart Kir6.2 protein and its immunohistochemical detection in myocytes were maximal at low venous PO(2). In the left ventricle the Kir6.2 protein/mRNA ratio was also significantly higher at low venous PO(2) suggesting that tissue hypoxia might stabilize the Kir6.2 protein. CONCLUSIONS Results suggest that post transcriptional events determine Kir6.2 protein expression in the left ventricle of patients with severe mitral dysfunction and low venous PO(2). Mechanical stress mainly affects transcription of HIF 1a and Kir6.2. This study implies that new therapies could aim at the proteasome for stabilizing the left ventricular Kir6.2 protein.

Published
2012

2. Impaired neoangiogenesis in β₂-adrenoceptor gene-deficient mice: restoration by intravascular human β₂-adrenoceptor gene transfer and role of NFκB and CREB transcription factors

Author

Ciccarelli, Michele, Sorriento, D., Cipolletta, E., Santulli, G., Fusco, A., Zhou, R., Eckhart, A. D., Peppel, K., Koch, W. J., Trimarco, B., and Iaccarino, Guido

Subjects
Male, Vascular Endothelial Growth Factor A, Cells, Knockout, Genetic Vectors, Neovascularization, Physiologic, beta-2, Transfection, Mice, Radioligand Assay, Ischemia, Receptors, deficiency/genetics/metabolism, Animals, Humans, Physiologic, Luciferases, Neovascularization, Cells, Cultured, Mice, Knockout, Cultured, Animal, NF-kappa B, Endothelial Cells, Gene Therapy, Genetic Therapy, CREB-Binding Protein, Research Papers, Disease Models, Animal, Adrenergic, Animals, Blood Flow Velocity, CREB-Binding Protein, metabolism, Cells, Cultured, Disease Models, Animal, Endothelial Cells, metabolism, Gene Therapy, Genetic Vectors, Humans, Ischemia, physiopathology/therapy, Luciferases, metabolism, Male, Mice, Mice, Knockout, NF-kappa B, metabolism, Neovascularization, Physiologic, Radioligand Assay, Receptors, deficiency/genetics/metabolism, Signal Transduction, Transfection, Vascular Endothelial Growth Factor A, metabolism, Disease Models, physiopathology/therapy, Receptors, Adrenergic, beta-2, Blood Flow Velocity, Signal Transduction
Abstract

There is much evidence supporting the role of β₂-adrenoceptors (β₂AR) in angiogenesis but the mechanisms underlying their effects have not been elucidated. Hence, we studied post-ischaemic angiogenesis in the hindlimb (HL) of β₂AR knock-out mice (β₂AR-/-) in vivo and explored possible molecular mechanisms in vitro.Femoral artery resection (FAR) was performed in wild-type and β₂AR-/- mice and adaptive responses to chronic HL ischaemia were explored; blood flow was measured by ultrasound and perfusion of dyed beads, bone rarefaction, muscle fibrosis and skin thickness were evaluated by immunoflourescence and morphometric analysis. Intrafemoral delivery of an adenovirus encoding the human β₂AR (ADβ₂AR) was used to reinstate β₂ARs in β₂AR-/- mice. Molecular mechanisms were investigated in mouse-derived aortic endothelial cells (EC) in vitro, focusing on NFκB activation and transcriptional activity.Angiogenesis was severely impaired in β₂AR-/- mice subjected to FAR, but was restored by gene therapy with ADβ₂AR. The proangiogenic responses to a variety of stimuli were impaired in β₂AR-/- EC in vitro. Moreover, removal of β₂ARs impaired the activation of NFκB, a transcription factor that promotes angiogenesis; neither isoprenaline (stimulates βARs) nor TNFα induced NFκB activation in β₂AR(-/-) EC. Interestingly, cAMP response element binding protein (CREB), a transcription factor that counter regulates NFκB, was constitutively increased in β₂AR(-/-) ECs. ADβ₂AR administration restored β₂AR membrane density, reduced CREB activity and reinstated the NFκB response to isoprenaline and TNFα.Our results suggest that β₂ARs control angiogenesis through the tight regulation of nuclear transcriptional activity.

Published
2010

3. Effects of immobilization stress on dopamine and its metabolites in different brain areas of the mouse: role of genotype and stress duration

Author

Simona Cabib, Carmen Schleff, Alberto Oliverio, Stefano Puglisi-Allegra, and Eliane Kempf

Subjects
Restraint, Physical, Male, medicine.medical_specialty, 4-Dihydroxyphenylacetic Acid, metabolism, Animals, Brain, metabolism, Dopamine, analogs /&/ derivatives/metabolism, Homovanillic Acid, metabolism, Male, Mice, Mice, Inbred C57BL, Mice, Inbred DBA, Organ Specificity, Restraint, Physical, Species Specificity, Stress, Psychological, physiopathology, Dopamine, Nucleus accumbens, Restraint, Inbred C57BL, Stress, chemistry.chemical_compound, Mice, Species Specificity, Internal medicine, analogs /&/ derivatives/metabolism, medicine, Physical, 3-Methoxytyramine, Animals, Inbred DBA, Molecular Biology, Strain (chemistry), Chemistry, General Neuroscience, Putamen, Dopaminergic, Homovanillic acid, Brain, Homovanillic Acid, Metabolism, Mice, Inbred C57BL, Endocrinology, Biochemistry, Mice, Inbred DBA, Organ Specificity, 3,4-Dihydroxyphenylacetic Acid, Neurology (clinical), metabolism, Stress, Psychological, Developmental Biology, medicine.drug
Abstract

Immobilization stress induced, in mice of both C57BL/6 (C57) and DBA/2 (DBA) strains, an increase in dihydroxyphenylacetic acid (DOPAC)/dopamine (DA) and homovanillic acid (HVA)/DA ratios and a reduction of 3-methoxytyramine (3-MT)/DA ratio in the caudatus putamen (CP) and nucleus accumbens septi (NAS). These effects were already evident after 30 min stress in the NAS, while in the CP 120 min were needed in order to show the effects of stress. Immobilization did not produce any effects on dopaminergic metabolism in the frontal cortex (FC) of the C57 strain either after 30 or after 120 min stress while in mice of the DBA strain a time-dependent effect of stress on the HVA/DA ratio was evident. When B6D2F1 hybrids were considered, the effects produced by 120 min immobilization in the CP and the NAS paralleled those observed in parental strains, while in the FC 120 min stress indcued the same increase of HVA observed in DBA mice, thus suggesting that the pattern of response in the FC that characterizes the DBA strain may be inherited through a dominant pattern of inheritance.

Published
1988

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