14 results on '"Valdez-Flores MA"'
Search Results
2. Chemical composition and physicochemical properties of Phaeodactylum tricornutum microalgal residual biomass
- Author
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German-Báez, LJ, primary, Valdez-Flores, MA, additional, Félix-Medina, JV, additional, Norzagaray-Valenzuela, CD, additional, Santos-Ballardo, DU, additional, Reyes-Moreno, C, additional, Shelton, LM, additional, and Valdez-Ortiz, A, additional
- Published
- 2017
- Full Text
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3. Antiviral Effect of Microalgae Phaeodactylum tricornutum Protein Hydrolysates against Dengue Virus Serotype 2.
- Author
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Rivera-Serrano BV, Cabanillas-Salcido SL, Cordero-Rivera CD, Jiménez-Camacho R, Norzagaray-Valenzuela CD, Calderón-Zamora L, De Jesús-González LA, Reyes-Ruiz JM, Farfan-Morales CN, Romero-Utrilla A, Ruíz-Ruelas VM, Camberos-Barraza J, Camacho-Zamora A, De la Herrán-Arita AK, Angulo-Rojo C, Guadrón-Llanos AM, Rábago-Monzón ÁR, Perales-Sánchez JXK, Valdez-Flores MA, Del Ángel RM, and Osuna-Ramos JF
- Subjects
- Animals, Protein Hydrolysates pharmacology, Protein Hydrolysates chemistry, Dengue drug therapy, Dengue virology, Peptides pharmacology, Peptides chemistry, Serogroup, Chlorocebus aethiops, Humans, Aedes drug effects, Vero Cells, Dengue Virus drug effects, Antiviral Agents pharmacology, Antiviral Agents chemistry, Microalgae
- Abstract
Dengue, caused by the dengue virus (DENV), is a global health threat transmitted by Aedes mosquitoes, resulting in 400 million cases annually. The disease ranges from mild to severe, with potential progression to hemorrhagic dengue. Current research is focused on natural antivirals due to challenges in vector control. This study evaluates the antiviral potential of peptides derived from the microalgae Phaeodactylum tricornutum , known for its bioactive compounds. Microalgae were cultivated under controlled conditions, followed by protein extraction and hydrolysis to produce four peptide fractions. These fractions were assessed for cytotoxicity via the MTT assay and antiviral activity against DENV serotype 2 using flow cytometry and plaque formation assays. The 10-30 kDa peptide fraction, at 150 and 300 μg/mL concentrations, demonstrated no cytotoxicity and significantly reduced the percentage of infected cells and viral titers. These findings suggest that peptides derived from Phaeodactylum tricornutum exhibit promising antiviral activity against dengue virus serotype 2, potentially contributing to developing new therapeutic approaches for dengue.
- Published
- 2024
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4. Chromosomal instability in a patient with ring chromosome 14 syndrome: a case report.
- Author
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Meza-Espinoza JP, González-García JR, Nieto-Marín N, Patrón-Baro LI, González-Arreola RM, Arámbula-Meraz E, Benítez-Pascual J, De la Herrán-Arita AK, Norzagaray-Valenzuela CD, Valdez-Flores MA, Carrillo-Cázares TA, and Picos-Cárdenas VJ
- Abstract
Background: Ring chromosome 14 syndrome is a rare disorder primarily marked by early-onset epilepsy, microcephaly, distinctive craniofacial features, hypotonia, intellectual disability, and delay in both development and language acquisition., Case Presentation: A 21-year-old woman with a history of epileptic seizures since the age of 1.5 years presented with distinctive craniofacial features, including a prominent and narrow forehead, sparse and short eyebrows, palpebral ptosis, horizontal palpebral fissures, a broad nasal bridge, a prominent nasal tip, a flat philtrum, hypertelorism, midfacial hypoplasia, horizontal labial fissures, a thin upper lip, crowded teeth, an ogival palate, retrognathia, and a wide neck. Additional physical abnormalities included kyphosis, lumbar scoliosis, pectus carinatum, cubitus valgus, thenar and hypothenar hypoplasia, bilateral hallux valgus, shortening of the Achilles tendon on the left foot, and hypoplasia of the labia minora. Chromosomal analysis identified a ring 14 chromosome with breakpoints in p11 and q32.33. An aCGH study revealed a ~ 1.7 Mb deletion on chromosome 14qter, encompassing 23 genes. Genomic instability was evidenced by the presence of micronuclei and aneuploidies involving the ring and other chromosomes., Conclusion: The clinical features of our patient closely resembled those observed in other individuals with ring chromosome 14 syndrome. The most important point was that we were able to verify an instability of the r(14) chromosome, mainly involving anaphasic lags and its exclusion from the nucleus in the form of a micronucleus., (© 2024. The Author(s).)
- Published
- 2024
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5. Association between lipid profile and clinical outcomes in COVID-19 patients.
- Author
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Ochoa-Ramírez LA, De la Herrán Arita AK, Sanchez-Zazueta JG, Ríos-Burgueño E, Murillo-Llanes J, De Jesús-González LA, Farfan-Morales CN, Cordero-Rivera CD, Del Ángel RM, Romero-Utrilla A, Camberos-Barraza J, Valdez-Flores MA, Camacho-Zamora A, Batiz-Beltrán JC, Angulo-Rojo C, Guadrón-Llanos AM, Picos-Cárdenas VJ, Norzagaray-Valenzuela CD, Rábago-Monzón ÁR, Velarde-Félix JS, Reyes-Ruiz JM, and Osuna-Ramos JF
- Subjects
- Humans, Male, Female, Middle Aged, Adult, Aged, Risk Factors, Triglycerides blood, Prognosis, Lipids blood, Mexico epidemiology, Dyslipidemias blood, Proportional Hazards Models, Hypertension blood, COVID-19 mortality, COVID-19 blood, Cholesterol, HDL blood, SARS-CoV-2 isolation & purification
- Abstract
High-density lipoprotein cholesterol (HDL-c) removes cholesterol, an essential component in lipid rafts, and this cholesterol removal can regulate protein attachment to lipid rafts, modulating their functionality in the immune cell response. Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can alter the lipid profile, there is little information on the role of HDL-c and other lipids in prognostic of the coronavirus disease 2019 (COVID-19) in Mexican population. This study aims to evaluate the predictive value of HDL-c and lipid profile on severity and survival of 102 patients infected with SARS-CoV-2 during the COVID-19 first wave. Our findings, derived from univariate and multivariate Cox proportional hazards regression models, highlighted age and hypertension as significant predictors of survival (HR = 1.04, p = 0.012; HR = 2.78, p = 0.027), while gender, diabetes, and obesity showed no significant impact. Triglycerides and HDL-c levels notably influenced mortality, with elevated triglycerides and lower HDL-c associated with higher mortality risk (p = 0.032). This study underscores the importance of lipid profiles alongside traditional risk factors in assessing COVID-19 risk and outcomes. It contributes to the understanding of COVID-19 patient management and emphasizes the need for further investigation into the role of dyslipidemia in influencing COVID-19 prognosis, potentially aiding in refined risk stratification and therapeutic strategies., (© 2024. The Author(s).)
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- 2024
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6. Sleep, Glial Function, and the Endocannabinoid System: Implications for Neuroinflammation and Sleep Disorders.
- Author
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Camberos-Barraza J, Camacho-Zamora A, Bátiz-Beltrán JC, Osuna-Ramos JF, Rábago-Monzón ÁR, Valdez-Flores MA, Angulo-Rojo CE, Guadrón-Llanos AM, Picos-Cárdenas VJ, Calderón-Zamora L, Norzagaray-Valenzuela CD, Cárdenas-Torres FI, and De la Herrán-Arita AK
- Subjects
- Humans, Neuroinflammatory Diseases, Central Nervous System, Sleep, Neuroglia, Endocannabinoids, Sleep Wake Disorders
- Abstract
The relationship between sleep, glial cells, and the endocannabinoid system represents a multifaceted regulatory network with profound implications for neuroinflammation and cognitive function. The molecular underpinnings of sleep modulation by the endocannabinoid system and its influence on glial cell activity are discussed, shedding light on the reciprocal relationships that govern these processes. Emphasis is placed on understanding the role of glial cells in mediating neuroinflammatory responses and their modulation by sleep patterns. Additionally, this review examines how the endocannabinoid system interfaces with glia-immune signaling to regulate inflammatory cascades within the central nervous system. Notably, the cognitive consequences of disrupted sleep, neuroinflammation, and glial dysfunction are addressed, encompassing implications for neurodegenerative disorders, mood disturbances, and cognitive decline. Insights into the bidirectional modulation of cognitive function by the endocannabinoid system in the context of sleep and glial activity are explored, providing a comprehensive perspective on the potential mechanisms underlying cognitive impairments associated with sleep disturbances. Furthermore, this review examines potential therapeutic avenues targeting the endocannabinoid system to mitigate neuroinflammation, restore glial homeostasis, and normalize sleep patterns. The identification of novel therapeutic targets within this intricate regulatory network holds promise for addressing conditions characterized by disrupted sleep, neuroinflammation, and cognitive dysfunction. This work aims to examine the complexities of neural regulation and identify potential avenues for therapeutic intervention.
- Published
- 2024
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7. Interplay between the Glymphatic System and the Endocannabinoid System: Implications for Brain Health and Disease.
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Osuna-Ramos JF, Camberos-Barraza J, Torres-Mondragón LE, Rábago-Monzón ÁR, Camacho-Zamora A, Valdez-Flores MA, Angulo-Rojo CE, Guadrón-Llanos AM, Picos-Cárdenas VJ, Calderón-Zamora L, Magaña-Gómez JA, Norzagaray-Valenzuela CD, Cárdenas-Torres FI, and De la Herrán-Arita AK
- Subjects
- Humans, Endocannabinoids metabolism, Brain metabolism, Central Nervous System, Glymphatic System metabolism, Nervous System Diseases metabolism
- Abstract
The intricate mechanisms governing brain health and function have long been subjects of extensive investigation. Recent research has shed light on two pivotal systems, the glymphatic system and the endocannabinoid system, and their profound role within the central nervous system. The glymphatic system is a recently discovered waste clearance system within the brain that facilitates the efficient removal of toxic waste products and metabolites from the central nervous system. It relies on the unique properties of the brain's extracellular space and is primarily driven by cerebrospinal fluid and glial cells. Conversely, the endocannabinoid system, a multifaceted signaling network, is intricately involved in diverse physiological processes and has been associated with modulating synaptic plasticity, nociception, affective states, appetite regulation, and immune responses. This scientific review delves into the intricate interconnections between these two systems, exploring their combined influence on brain health and disease. By elucidating the synergistic effects of glymphatic function and endocannabinoid signaling, this review aims to deepen our understanding of their implications for neurological disorders, immune responses, and cognitive well-being.
- Published
- 2023
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8. Scientific facts improve cannabis perception and public opinion: results from Sinaloa, México.
- Author
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Camberos-Barraza J, Osuna-Ramos JF, Rábago-Monzón ÁR, Quiñonez-Angulo LF, González-Peña HR, Pérez-Ramos AA, Camacho-Zamora A, López-Lazcano H, Valdez-Flores MA, Angulo-Rojo CE, Guadrón-Llanos AM, Picos-Cárdenas VJ, Norzagaray-Valenzuela CD, and De la Herrán-Arita AK
- Subjects
- Humans, Public Opinion, Mexico, Attitude, Cannabinoid Receptor Agonists, Perception, Cannabis, Hallucinogens
- Abstract
Cannabis, the most prevalent drug in Latin America, has long been associated with the state of Sinaloa, Mexico, known for its cultivation and distribution. Despite increasing global acceptance, cannabis use remains stigmatized in Mexican society, driven by perceptions of it as a highly psychoactive and addictive substance lacking medicinal or industrial value. This study investigates the impact of scientific information on societal perceptions of cannabis in Sinaloa. A large convenience sample of 3162 individuals from Sinaloa participated in this research, responding to a questionnaire on cannabis consumption and attitudes. Participants were then subjected to an intervention consisting of an informative briefing based on the documents "Using Evidence to Talk About Cannabis" and "State of the Evidence: cannabis use and regulation" by the International Centre for Science in Drug Policy. After the intervention, participants' attitudes were immediately reevaluated through the same questionnaire, allowing for a comparison of pre- and post-intervention responses. The results indicate that the intervention (providing scientific information) significantly influenced attitudes toward cannabis, with education and age playing prominent roles in its effectiveness. Notably, the intervention fostered more positive or more neutral attitudes, potentially reducing stigma and promoting a better-informed perspective on cannabis. This study highlights the pivotal role of evidence in shaping informed citizens' views, while underscoring the importance of countering misinformation for societal progress. These findings have significant implications for forthcoming cannabis policy modifications in Mexico, emphasizing the necessity of engaging knowledgeable individuals in policy decisions to address the violence and inequalities associated with the illicit drug trade, particularly in Sinaloa., (© 2023. Springer Nature Limited.)
- Published
- 2023
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9. Clinical Predictors of Monkeypox Diagnosis: A Case-Control Study in a Nonendemic Region during the 2022 Outbreak.
- Author
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De la Herrán-Arita AK, González-Galindo C, Inzunza-Leyva GK, Valdez-Flores MA, Norzagaray-Valenzuela CD, Camacho-Zamora A, Batiz-Beltrán JC, Urrea-Ramírez FJ, Romero-Utrilla A, Angulo-Rojo C, Guadrón-Llanos AM, Picos-Cárdenas VJ, Camberos-Barraza J, Rábago-Monzón ÁR, and Osuna-Ramos JF
- Abstract
Monkeypox (Mpox) is an emerging zoonotic disease with the potential for severe complications. Early identification and diagnosis are essential to prompt treatment, control its spread, and reduce the risk of human-to-human transmission. This study aimed to develop a clinical diagnostic tool and describe the clinical and sociodemographic features of 19 PCR-confirmed Mpox cases during an outbreak in a nonendemic region of northwestern Mexico. The median age of patients was 35 years, and most were male. Mpox-positive patients commonly reported symptoms such as fever, lumbago, and asthenia, in addition to experiencing painful ulcers and a high frequency of HIV infection among people living with HIV (PLWH). Two diagnostic models using logistic regression were devised, with the best model exhibiting a prediction accuracy of 0.92 (95% CI: 0.8-1), a sensitivity of 0.86, and a specificity of 0.93. The high predictive values and accuracy of the top-performing model highlight its potential to significantly improve early Mpox diagnosis and treatment in clinical settings, aiding in the control of future outbreaks.
- Published
- 2023
- Full Text
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10. Detection of antimicrobial-resistance diarrheagenic Escherichia coli strains in surface water used to irrigate food products in the northwest of Mexico.
- Author
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Canizalez-Roman A, Velazquez-Roman J, Valdez-Flores MA, Flores-Villaseñor H, Vidal JE, Muro-Amador S, Guadrón-Llanos AM, Gonzalez-Nuñez E, Medina-Serrano J, Tapia-Pastrana G, and León-Sicairos N
- Subjects
- Anti-Bacterial Agents pharmacology, Diarrhea microbiology, Drug Resistance, Multiple, Bacterial, Enteropathogenic Escherichia coli drug effects, Enterotoxigenic Escherichia coli drug effects, Escherichia coli Infections epidemiology, Escherichia coli Infections microbiology, Foodborne Diseases microbiology, Humans, Mexico epidemiology, Water, Water Microbiology, Waterborne Diseases microbiology, Agricultural Irrigation methods, Enteropathogenic Escherichia coli isolation & purification, Enterotoxigenic Escherichia coli isolation & purification, Rivers microbiology, Water Quality
- Abstract
Water contamination by pathogenic bacteria is a global public health problem. Contamination of surface water utilized to irrigate food products, or for human consumption, causes outbreaks of foodborne and waterborne disease. Of these, those caused by diarrheagenic Escherichia coli (DEC) strains present substantial morbidity and mortality. The aim of this study was, therefore, to investigate the microbiological quality of surface water and the presence of DEC strains in different water bodies. A total of 472 water samples were collected from irrigation canal, dam, river, and dike water bodies from January through December 2015 in Sinaloa, a State located in Northwestern Mexico. Our studies demonstrated that 47.0% (222/472) of samples contained thermotolerant coliforms above permissive levels whereas E. coli strains were isolated from 43.6% (206/472). Among these E. coli isolates, DEC strains were identified in 14% (29/206) of samples including in irrigation canal (26/29) and river water (3/29) collected from the northern (83%) and central area (17%). Isolated DEC strains were classified as enteroaggregative E. coli (EAEC) 34.4% (10/29), enteropathogenic E. coli (EPEC) 31.0% (9/29), diffuse adherent E. coli (DAEC) 27.5% (8/29), and enterotoxigenic E. coli (ETEC) 6.8% (2/29). Moreover, 90% of isolated DEC strains exhibited resistance to at least one commonly prescribed antibiotic in Mexico whereas 17% were multi-drug resistant. In conclusion, the presence of DEC strains in surface water represents a potential source for human infection, and thus routine monitoring of DEC in surface water and other indirect affected areas should be considered at northwestern Mexico., (Copyright © 2019 Elsevier B.V. All rights reserved.)
- Published
- 2019
- Full Text
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11. Establishment of an efficient genetic transformation method in Dunaliella tertiolecta mediated by Agrobacterium tumefaciens.
- Author
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Norzagaray-Valenzuela CD, Germán-Báez LJ, Valdez-Flores MA, Hernández-Verdugo S, Shelton LM, and Valdez-Ortiz A
- Subjects
- Anti-Bacterial Agents pharmacology, Cell Survival, Chlorophyceae drug effects, Chlorophyceae growth & development, Coculture Techniques, Gene Expression Regulation, Plant, Genes, Plant genetics, Genetic Vectors, Hygromycin B pharmacology, Kinetics, Microalgae growth & development, Plants, Genetically Modified, Polymerase Chain Reaction, Agrobacterium tumefaciens genetics, Chlorophyceae genetics, Microalgae genetics, Transformation, Genetic
- Abstract
Microalgae are photosynthetic microorganisms widely used for the production of highly valued compounds, and recently they have been shown to be promising as a system for the heterologous expression of proteins. Several transformation methods have been successfully developed, from which the Agrobacterium tumefaciens-mediated method remains the most promising. However, microalgae transformation efficiency by A. tumefaciens is shown to vary depending on several transformation conditions. The present study aimed to establish an efficient genetic transformation system in the green microalgae Dunaliella tertiolecta using the A. tumefaciens method. The parameters assessed were the infection medium, the concentration of the A. tumefaciens and co-culture time. As a preliminary screening, the expression of the gusA gene and the viability of transformed cells were evaluated and used to calculate a novel parameter called Transformation Efficiency Index (TEI). The statistical analysis of TEI values showed five treatments with the highest gusA gene expression. To ensure stable transformation, transformed colonies were cultured on selective medium using hygromycin B and the DNA of resistant colonies were extracted after five subcultures and molecularly analyzed by PCR. Results revealed that treatments which use solid infection medium, A. tumefaciens OD
600 = 0.5 and co-culture times of 72 h exhibited the highest percentage of stable gusA expression. Overall, this study established an efficient, optimized A. tumefaciens-mediated genetic transformation of D. tertiolecta, which represents a relatively easy procedure with no expensive equipment required. This simple and efficient protocol opens the possibility for further genetic manipulation of this commercially-important microalgae for biotechnological applications., (Copyright © 2018 Elsevier B.V. All rights reserved.)- Published
- 2018
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12. Prospective comparison among three intrarectal anesthetic treatments combined with periprostatic nerve block during transrectal ultrasonography-guided prostate biopsy.
- Author
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Valdez-Flores RA, Campos-Salcedo JG, Torres-Gomez JJ, Sedano-Lozano A, Parés-Hipólito J, Shelton LM, Canizalez-Román A, and Valdez-Flores MA
- Subjects
- Administration, Topical, Aged, Anesthesia, Local methods, Biopsy, Large-Core Needle methods, Endosonography methods, Humans, Image-Guided Biopsy methods, Lidocaine, Prilocaine Drug Combination, Male, Middle Aged, Pain Measurement, Rectum, Anesthetics, Local therapeutic use, Anti-Inflammatory Agents, Non-Steroidal therapeutic use, Indomethacin therapeutic use, Lidocaine therapeutic use, Nerve Block methods, Pain, Procedural prevention & control, Prilocaine therapeutic use, Prostate pathology
- Abstract
Background: Recent trends in prostate biopsy analgesia suggest a combination anesthetic to provide better pain relief than periprostatic nerve block (PPNB) alone. This study aimed to demonstrate the efficacy and safety of three intrarectal local anesthesia (IRLA) combined with PPNB in patients undergoing transrectal ultrasonography (TRUS)-guided prostate biopsy., Methods: In this prospective, randomized study, 120 prostate biopsy patients were equally divided into four IRLA groups: group 1 (placebo) received simple lubrication; group 2 received 2% lidocaine gel; group 3 received 100 mg indomethacin suppository and group 4 received 5% prilocaine/lidocaine (EMLA) cream. PPNB with 2% lidocaine was applied in all groups. A ten-point visual analog scale evaluated both pain associated with the probe insertion and pain associated with prostate sampling. Adverse effects or complications due to anesthesia during and after the procedure were documented., Results: Compared with group 1, groups 3 and 4 had significantly lower pain scores at both probe insertion and prostate sampling while group 2 showed no significant differences at both pain scores. Moreover, group 4 showed significantly lower pain scores at probe insertion compared to group 3, while no significant difference was observed at prostate sampling. Mild complications were observed in all groups with no significant difference in the incidence of complications between groups., Conclusion: Intrarectal application of EMLA cream is a more efficient pain reduction than either 2% lidocaine gel or 100 mg indomethacin suppository when applied combined with PPNB. This combination represents an effective option of pain relief for patients undergoing TRUS-guided prostate biopsy.
- Published
- 2018
- Full Text
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13. NaCl cotransporter abundance in urinary vesicles is increased by calcineurin inhibitors and predicts thiazide sensitivity.
- Author
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Tutakhel OAZ, Moes AD, Valdez-Flores MA, Kortenoeven MLA, Vrie MVD, Jeleń S, Fenton RA, Zietse R, Hoenderop JGJ, Hoorn EJ, Hilbrands L, and Bindels RJM
- Subjects
- Animals, Case-Control Studies, Cohort Studies, Humans, Mice, Mice, Inbred C57BL, Calcineurin Inhibitors pharmacology, Sodium Chloride Symporters metabolism, Thiazides pharmacology
- Abstract
Animal studies have shown that the calcineurin inhibitors (CNIs) cyclosporine and tacrolimus can activate the thiazide-sensitive NaCl cotransporter (NCC). A common side effect of CNIs is hypertension. Renal salt transporters such as NCC are excreted in urinary extracellular vesicles (uEVs) after internalization into multivesicular bodies. Human studies indicate that CNIs also increase NCC abundance in uEVs, but results are conflicting and no relationship with NCC function has been shown. Therefore, we investigated the effects of CsA and Tac on the abundance of both total NCC (tNCC) and phosphorylated NCC at Thr60 phosphorylation site (pNCC) in uEVs, and assessed whether NCC abundance in uEVs predicts the blood pressure response to thiazide diuretics. Our results show that in kidney transplant recipients treated with cyclosporine (n = 9) or tacrolimus (n = 23), the abundance of both tNCC and pNCC in uEVs is 4-5 fold higher than in CNI-free kidney transplant recipients (n = 13) or healthy volunteers (n = 6). In hypertensive kidney transplant recipients, higher abundances of tNCC and pNCC prior to treatment with thiazides predicted the blood pressure response to thiazides. During thiazide treatment, the abundance of pNCC in uEVs increased in responders (n = 10), but markedly decreased in non-responders (n = 8). Thus, our results show that CNIs increase the abundance of both tNCC and pNCC in uEVs, and these increases correlate with the blood pressure response to thiazides. This implies that assessment of NCC in uEVs could represent an alternate method to guide anti-hypertensive therapy in kidney transplant recipients.
- Published
- 2017
- Full Text
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14. Functionomics of NCC mutations in Gitelman syndrome using a novel mammalian cell-based activity assay.
- Author
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Valdez-Flores MA, Vargas-Poussou R, Verkaart S, Tutakhel OA, Valdez-Ortiz A, Blanchard A, Treard C, Hoenderop JG, Bindels RJ, and Jeleń S
- Subjects
- Biological Assay methods, Gitelman Syndrome metabolism, Glycosylation, HEK293 Cells, Humans, Mutation, Phosphorylation, Solute Carrier Family 12, Member 3 metabolism, Gitelman Syndrome genetics, Solute Carrier Family 12, Member 3 genetics
- Abstract
Gitelman syndrome (GS) is an autosomal recessive salt-wasting tubular disorder resulting from loss-of-function mutations in the thiazide-sensitive NaCl cotransporter (NCC). Functional analysis of these mutations has been limited to the use of Xenopus laevis oocytes. The aim of the present study was, therefore, to analyze the functional consequences of NCC mutations in a mammalian cell-based assay, followed by analysis of mutated NCC protein expression as well as glycosylation and phosphorylation profiles using human embryonic kidney (HEK) 293 cells. NCC activity was assessed with a novel assay based on thiazide-sensitive iodide uptake in HEK293 cells expressing wild-type or mutant NCC (N59I, R83W, I360T, C421Y, G463R, G731R, L859P, or R861C). All mutations caused a significantly lower NCC activity. Immunoblot analysis of the HEK293 cells revealed that 1) all NCC mutants have decreased NCC protein expression; 2) mutant N59I, R83W, I360T, C421Y, G463R, and L859P have decreased NCC abundance at the plasma membrane; 3) mutants C421Y and L859P display impaired NCC glycosylation; and 4) mutants N59I, R83W, C421Y, C731R, and L859P show affected NCC phosphorylation. In conclusion, we developed a mammalian cell-based assay in which NCC activity assessment together with a profiling of mutated protein processing aid our understanding of the pathogenic mechanism of the NCC mutations., (Copyright © 2016 the American Physiological Society.)
- Published
- 2016
- Full Text
- View/download PDF
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