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Cumulative Effect of Cardiovascular Risk Factors on Regulation of AMPK/SIRT1-PGC-1α-SIRT3 Pathway in the Human Erectile Tissue

التفاصيل البيبلوغرافية
العنوان: Cumulative Effect of Cardiovascular Risk Factors on Regulation of AMPK/SIRT1-PGC-1α-SIRT3 Pathway in the Human Erectile Tissue
المؤلفون: Adriana Rodrigues, Nuno Tomada, Andressa S Pereira, Delminda Neves, Alexandra Gouveia
المساهمون: Instituto de Investigação e Inovação em Saúde, Faculdade de Medicina
المصدر: Repositório Científico de Acesso Aberto de Portugal
Repositório Científico de Acesso Aberto de Portugal (RCAAP)
instacron:RCAAP
Oxidative Medicine and Cellular Longevity, Vol 2020 (2020)
بيانات النشر: Hindawi, 2020.
سنة النشر: 2020
مصطلحات موضوعية: 0301 basic medicine, Adult, Male, Aging, Cardiovascular Diseases / metabolism, Article Subject, Cardiovascular risk factors, Erectile tissue, 030204 cardiovascular system & hematology, Biochemistry, 03 medical and health sciences, 0302 clinical medicine, Sirtuin 1 / metabolism, Erectile Dysfunction / metabolism, medicine, Humans, AMP-Activated Protein Kinases / metabolism, Biological sciences, Cumulative effect, QH573-671, business.industry, Health sciences, Medical and Health sciences, Ciências médicas e da saúde, AMPK, Cell Biology, General Medicine, Middle Aged, Molecular biology, Sirtuin 3 / metabolism, 030104 developmental biology, medicine.anatomical_structure, Heart Disease Risk Factors, Medical and Health sciences, Ciências da Saúde, Ciências médicas e da saúde, Cytology, business, Signal Transduction
الوصف: Cardiovascular disease risk factors (CVDRF), especially diabetes mellitus (DM), disrupt oxidative stress response. This condition underlies endothelial dysfunction, early manifested in men as erectile dysfunction. The current study is aimed at elucidating the impact of CVDRF in the oxidation responsive AMPK/SIRT1-PGC-1α-SIRT3 pathway and related miRNAs in the human corpus cavernosum. Human penile tissue fragments from individuals submitted to programmed urological surgeries (n=27), aged 43-63 years, were clustered depending on the presence of CVDRF; the control group included samples from patients without CVDRF, and groups A and B included samples from patients with DM and additional CVDRF, totalizing ≤2 CVDRF (group A) and ≥3 CVDRF (group B). Dual-immunolabelling of SIRT3, SOD2, or GPX1 with α-actin in tissue sections was carried out. The assessment of expression levels of NOX1, phospho-AMPKα, total AMPKα, SIRT1, PGC-1α, SIRT3, SOD2, and GPX1 was performed by western blotting and of miR-200a, miR-34a, miR-421, and miR-206 by real-time PCR. Phospho-AMPKα and SIRT3 expression was found significantly increased in group B relative to other groups, suggesting a marked influence of CVDRF, additional to DM, in the regulation of these enzymes. NOX1 was also increased in group B relative to controls. Only an increasing tendency was observed in the phospho-AMPKα/total AMPKα ratio, SIRT1, and PGC-1α expression in groups A and B when compared with controls. Concerning antioxidant enzymes, GPX1 expression was found incremented in group A, but SOD2 expression was decreased in groups A and B, comparative with controls. Group B presented significantly diminished levels of miR-421 and miR-200a, but only a decreasing trend on miR-34 and miR-206 expression was observed. Taken together, our findings demonstrated that besides DM, additional CVDRF presented a cumulative effect in the cellular response to oxidative unbalance, contributing to AMPK/SIRT1-PGC-1α-SIRT3 pathway activation. SOD2, a major mitochondrial antioxidant defence, did not follow the same variation.
وصف الملف: text/xhtml; application/pdf
اللغة: English
تدمد: 1942-0900
DOI: 10.1155/2020/1525949
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::63c615583ad0a1dc43fc714c0c1bd488
حقوق: OPEN
رقم الأكسشن: edsair.doi.dedup.....63c615583ad0a1dc43fc714c0c1bd488
قاعدة البيانات: OpenAIRE
الوصف
تدمد:19420900
DOI:10.1155/2020/1525949