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

• Published in: Canadian journal of physiology and pharmacology Vol. 96; no. 3; pp. 266 - 274
• Main Authors: Muniz, Jaqueline J, Leite, Letícia N, Lacchini, Riccardo, Tanus-Santos, José E, Tirapelli, Carlos R
• Format: Journal Article
• Language: English
• Published: Canada NRC Research Press 01.03.2018; Canadian Science Publishing NRC Research Press
• Subjects: Animal models; cavernosal smooth muscle; Cavernous hemangioma; Contraction; Endothelin 1; endothéline-1; Ethanol; Extracellular signal-regulated kinase; Gelatinase A; Gelatinase B; Health aspects; Immunoblotting; Kinases; MAP kinase; MAP kinases; Matrix metalloproteinase; metalloproteinases; Metalloproteins; Mitogen-activated protein kinases; mRNA; muscle lisse caverneux; métalloprotéinases; Pharmacology; Phosphorylation; Physiological aspects; Physiology; Polymerase chain reaction; Protein kinase; Proteins; Smooth muscle; Tissue inhibitor of metalloproteinase 1; Tissue inhibitor of metalloproteinase 2; mitogen-activated protein kinases; MAP kinases; metalloproteinases; muscle lisse caverneux; endothéline-1; endothelin-1; ethanol; cavernosal smooth muscle; métalloprotéinases
• ISSN: 0008-4212; 1205-7541; 1205-7541
• DOI: 10.1139/cjpp-2017-0082

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.