Autor(es)

Ghezzi, Ana Carolina ; Passos, Gabriela Reolon ; de Oliveira, Mariana Goncalves ; Oliveira, Akila Lara ; Assis-Mendonca, Guilherme Rossi ; de Mello, Glaucia Coelho ; Antunes, Edson ; Monica, Fabiola Zakia

• Tipo de documento: Artigo Científico
• Fonte: Clinical and Experimental Pharmacology and Physiology; v. 51, n. 4, p. 11-pg., 2024-04-01.

Resumo

Benign prostatic hyperplasia (BPH) is characterised by increases in prostate volume and contraction. Downregulation of the nitric oxide (NO)-cyclic guanosine monophosphate (cGMP) signalling pathway contributes to prostate dysfunctions. Previous studies in cancer cells or vessels have shown that the epigenetic mechanisms control the gene and protein expression of the enzymes involved in the production of NO and cGMP. This study is aimed to evaluate the effect of a 2-week treatment of 5-azacytidine (5-AZA), a DNA-methyltransferase inhibitor, in the prostate function of mice fed with a high-fat diet. Functional, histological, biochemical and molecular assays were carried out. Obese mice presented greater prostate weight, alpha-actin expression and contractile response induced by the alpha-1adrenoceptors agonist. The relaxation induced by the NO-donor and the protein expression of endothelial nitric oxide synthase (eNOS) and soluble guanylate cyclase (sGC) were significantly decreased in the prostate of obese mice. The treatment with 5-AZA reverted the higher expression of alpha-actin, reduced the hypercontractility state of the prostate and increased the expression of eNOS and sGC and intraprostatic levels of cGMP. When prostates from obese mice treated with 5-AZA were incubated in vitro with inhibitors of the NOS or sGC, the inhibitory effect of 5-AZA was reverted, therefore, showing the involvement of NO and cGMP. In conclusion, our study paves the way to develop or repurpose therapies that recover the expression of eNOS and sGC and, hence, to improve prostate function in BPH. (AU)

• Processo FAPESP: 19/19490-4 - Avaliação do efeito de inibidores da histona deacetilase e DNA-metiltransferase e do ativador da sirtuína-1 na via NO-GCs-GMPc no tecido vesical, uretral e prostático em condições fisiológicas e patológicas (obesidade e cistite).
• Beneficiário: Ana Carolina Ghezzi Beghini
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 17/15175-1 - Modulação da guanilato ciclase solúvel e dos níveis intracelulares de nucleotídeos cíclicos em órgãos do trato urinário inferior e próstata
• Beneficiário: Edson Antunes
• Modalidade de apoio: Auxílio à Pesquisa - Temático