PS071
Intervention of diabetes mellitus and metabolic risk factors in AMPK-PGC1α-SIRT3 pathway in the human corpus cavernosum
A. Santos Pereira1,3,, , A.R. Rodrigues1, B. Rocha1, N. Tomada2, A.M. Gouveia1,4, D. Neves1
1 Department of Biomedicine - Experimental Biology Unit, Faculty of Medicine of the University of Porto, Al. Prof. Hernâni Monteiro, 4200-319 Porto, Portugal and Instituto de Investigação e Inovação em Saúde (I3S) Rua Alfredo Allen, 208, 4200-135 Porto, Portugal
2 Department of Urology, Central Hospital of S. João- Alameda Prof. Hernâni Monteiro, 4200-319 Porto, Portugal
3 Faculty of Medicine, University of Porto, Portugal
4 Faculty of Nutrition and Food Sciences, University of Porto, Portugal

Aim: This study aims to investigate the signaling pathway AMP-activated protein kinase (AMPK)-Peroxisome proliferator-activated receptor-gamma coactivator (PGC)1α-sirtuin (SIRT)3 in the human corpus cavernosum (HCC) between healthy individuals and those with cardiovascular disease risk factors (CVDRF).

Introduction: SIRT3 is a mitochondrial NAD+-dependent-protein-deacetylase involved in the regulation of cellular metabolism.1,2 As a key factor in AMPK and PGC1-α activation in stress, the decrease in SIRT3 expression or activity is associated with diverse pathologies and aging. Actually, SIRT3 expression was found decreased in HCC of aged individuals with CVDRF.3 CVDRF such as diabetes mellitus (DM), dyslipidemia, hypertension and obesity strongly associate to endothelial dysfunction, which early manifests as erectile dysfunction (ED).4

Methods: HCC's samples from individuals aged 40-60 years, submitted to programmed urological surgeries at Hospital São João-Porto, were divided in three groups (n=4): (1)-controls without ED or CVDRF; (2)-DM patients; and (3)-patients with three or more CVDRF including DM. Dual immunolabelling of SIRT3 and superoxide dismutase (SOD)2 with alpha-actin was carried out. As well, levels of SIRT1, SIRT3, SOD2, PGC1α, NADPH oxidase (Nox)1, phospho-AMPK and AMPK were assessed by Western-blotting(WB).

Results: We observed SIRT3 and SOD2 expression in α-actin-labelled fusiform muscle cells in all groups. The semi-quantification by WB demonstrated a significant decrease in SOD2 expression in group 3 relatively to controls, as well as, an increased tendency of Nox1 and PGC1α and a decreasing trend in phospho-AMPK in groups 2 and 3. No differences in SIRT1 and SIRT3 were observed among groups.

Conclusion: This study suggests that CVRF including DM increase oxidative stress in HCC owning to a decrease in SOD2 expression and concomitant increment in Nox1. Further studies with an increased number of HCC samples will be necessary to elucidate the role of the AMPK-PGC1α-SIRT3 signaling pathway in the response to oxidative damage.5

Acknowledgements: Adriana R Rodrigues was supported by QREN-POPH, FSE and “Fundação para a Ciência e Tecnologia” (SFRH/BPD/92868/2013).

References
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R.A. Frye
Characterization of five human cDNAs with homology to the yeast SIR2 gene: Sir2-like proteins (sirtuins) metabolize NAD and may have protein ADP-ribosyltransferase activity
Biochem Biophys Res Commun, 260 (1999), pp. 273-279 http://dx.doi.org/10.1006/bbrc.1999.0897
2
B. Schwer
The human silent information regulator (Sir)2 homologue hSIRT3 is a mitochondrial nicotinamide adenine dinucleotide-dependent deacetylase
J Cell Biol, 158 (2002), pp. 647-657 http://dx.doi.org/10.1083/jcb.200205057
PMC
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M. Freitas
Effects of aging and cardiovascular disease risk factors on the expression of sirtuins in the human corpus cavernosum
J Sex Med, 12 (2015), pp. 2141-2152 http://dx.doi.org/10.1111/jsm.13035
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A.T. Guay
ED2: erectile dysfunction=endothelial dysfunction
Endocrinol Metab Clin North Am, 36 (2007), pp. 453-463 http://dx.doi.org/10.1016/j.ecl.2007.03.007
5
L. Yu
Melatonin ameliorates myocardial ischemia/reperfusion injury in type 1 diabetic rats by preserving mitochondrial function: role of AMPK-PGC-1α-SIRT3 signaling

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