Dysregulated mitogen-activated protein kinase and matrix metalloproteinase in ethanol-induced cavernosal dysfunction

Autor(es)

Muniz, Jaqueline J. ^[1] ; Leite, Leticia N. ^{[2, 1]} ; Lacchini, Riccardo ^[1] ; Tanus-Santos, Jose E. ^[2] ; Tirapelli, Carlos R. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, DEPCH, Escola Enfermagem Ribeirao Preto, Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Farmacol, Ribeirao Preto, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Canadian Journal of Physiology and Pharmacology; v. 96, n. 3 MAR 2018.
• Citações Web of Science: 1

Resumo

We evaluated the effects of ethanol consumption on the mitogen-activated protein kinases (MAPK) and metalloproteinases (MMP) pathways in the rat cavernosal smooth muscle (CSM). Male Wistar rats were treated with ethanol (20% v/v) for 6 weeks. Quantitative real-time polymerase chain reaction experiments showed that ethanol consumption did not alter mRNA levels of p38MAPK, SAPK/JNK, ERK1/2, MMP-2, or MMP-9 in the rat CSM. Western immunoblotting experiments revealed decreased protein expression of p38MAPK and phosphorylation of SAPK/JNK in the CSM from ethanol-treated rats. Additionally, ethanol consumption decreased the expression of MMP-2. Functional assays showed that SP600125, an inhibitor of SAPK/JNK, prevented the increase in endothelin (ET)-1-induced contraction in the CSM from ethanol-treated rats. Treatment with ethanol decreased MMP-2 activity, but did not change net MMP activity in the rat CSM. Ethanol consumption increased the circulating levels of MMP-2, MMP-9, and TIMP-2 as well as the MMP-9/TIMP-1 ratio. The major finding of our study is that ethanol consumption down-regulates both MAPK and MMP pathways in the rat CSM, whereas it increases the circulating levels of MMP-9. Additionally, we found that SAPK/JNK plays a role in ethanol-induced increase on ET-1 contraction in the isolated rat CSM. (AU)

• Processo FAPESP: 12/04144-4 - Consequências do consumo crônico de etanol sobre a via das metaloproteinases e MAPKs e sobre o remodelamento tecidual em corpo cavernoso de ratos.
• Beneficiário: Jaqueline Jóice Muniz
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 11/12911-2 - Consequências do consumo crônico de etanol sobre a reatividade e expressão dos componentes do sistema endotelinérgico em corpo cavernoso de rato
• Beneficiário: Carlos Renato Tirapelli
• Modalidade de apoio: Auxílio à Pesquisa - Regular