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

被引：3

作者：

Muniz, Jaqueline J. ^{[1
]}

Leite, Leticia N. ^{[1
,2
]}

Lacchini, Riccardo ^{[1
]}

Tanus-Santos, Jose E. ^{[2
]}

Tirapelli, Carlos R. ^{[1
]}

机构：

[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

来源：

CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY | 2018年 / 96卷 / 03期

关键词：

ethanol; endothelin-1; mitogen-activated protein kinases; metalloproteinases; cavernosal smooth muscle; ALCOHOL-DEPENDENT MEN; QUALITY-OF-LIFE; SMOOTH-MUSCLE; CONSUMPTION INCREASES; ERECTILE DYSFUNCTION; INDUCED HYPERTENSION; TISSUE INHIBITORS; OXIDATIVE STRESS; RAT AORTA; PATHWAY;

D O I：

10.1139/cjpp-2017-0082

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

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.

引用

页码：266 / 274

页数：9