Cumulative Effect of Cardiovascular Risk Factors on Regulation of AMPKSIRT1-PGC-1α-SIRT3 Pathway in the Human Erectile Tissue
Joint Authors
Neves, Delminda
Gouveia, Alexandra Monteiro
Pereira, Andressa S.
Rodrigues, Adriana R.
Tomada, Nuno
Source
Oxidative Medicine and Cellular Longevity
Issue
Vol. 2020, Issue 2020 (31 Dec. 2020), pp.1-10, 10 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2020-04-23
Country of Publication
Egypt
No. of Pages
10
Main Subjects
Abstract EN
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.
American Psychological Association (APA)
Pereira, Andressa S.& Gouveia, Alexandra Monteiro& Tomada, Nuno& Rodrigues, Adriana R.& Neves, Delminda. 2020. Cumulative Effect of Cardiovascular Risk Factors on Regulation of AMPKSIRT1-PGC-1α-SIRT3 Pathway in the Human Erectile Tissue. Oxidative Medicine and Cellular Longevity،Vol. 2020, no. 2020, pp.1-10.
https://search.emarefa.net/detail/BIM-1203746
Modern Language Association (MLA)
Pereira, Andressa S.…[et al.]. Cumulative Effect of Cardiovascular Risk Factors on Regulation of AMPKSIRT1-PGC-1α-SIRT3 Pathway in the Human Erectile Tissue. Oxidative Medicine and Cellular Longevity No. 2020 (2020), pp.1-10.
https://search.emarefa.net/detail/BIM-1203746
American Medical Association (AMA)
Pereira, Andressa S.& Gouveia, Alexandra Monteiro& Tomada, Nuno& Rodrigues, Adriana R.& Neves, Delminda. Cumulative Effect of Cardiovascular Risk Factors on Regulation of AMPKSIRT1-PGC-1α-SIRT3 Pathway in the Human Erectile Tissue. Oxidative Medicine and Cellular Longevity. 2020. Vol. 2020, no. 2020, pp.1-10.
https://search.emarefa.net/detail/BIM-1203746
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1203746