Title

P38 And Erk1/2 Mapks Mediate The Interplay Of Tnf-Α And Il-10 In Regulating Oxidative Stress And Cardiac Myocyte Apoptosis

Keywords

Cell communication; Heart failure; Mitogen-activated protein kinase; Signal transduction

Abstract

It is known that TNF-α increases the production of ROS and decreases antioxidant enzymes, resulting in an increase in oxidative stress. IL-10 appears to modulate these effects. The present study investigated the role of p38 and ERK1/2 MAPKs in mediating the interplay of TNF-α and IL-10 in regulating oxidative stress and cardiac myocyte apoptosis in Sprague-Dawley male rats. Isolated adult cardiac myocytes were exposed to TNF-α (10 ng/ml), IL-10 (10 ng/ml), and IL-10 + TNF-α (ratio 1) for 4 h. H2O 2 (100 μM) as a positive control and the antioxidant Trolox (20 μmol/l) were used to confirm the involvement of oxidative stress. H 2O2 treatment increased oxidative stress and apoptosis; TNF-α mimicked these effects. Exposure to TNF-α significantly increased ROS production, caused cell injury, and increased the number of apoptotic cells and Bax-to-Bcl-xl ratio. This change was associated with an increase in the phospho-p38 MAPK-to-total p38 MAPK ratio and a decrease in the phospho-ERK1/2-to-total ERK1/2 ratio. IL-10 treatment by itself had no effect on these parameters, but it prevented the above-listed changes caused by TNF-α. The antioxidant Trolox modulated TNF-α-induced changes in Bax/Bcl-xl, cell injury, and MAPKs. Preexposure of cells to the p38 MAPK inhibitor SB-203580 prevented TNF-α-induced changes. Inhibition of the ERK pathway with PD-98059 attenuated the protective role of IL-10 against TNF-α-induced apoptosis. This study provides evidence in support of the essential role of p38 and ERK1/2 MAPKs in the interactive role of TNF-α and IL-10 in cardiac myocyte apoptosis. Copyright © 2007 the American Physiological Society.

Publication Date

12-1-2007

Publication Title

American Journal of Physiology - Heart and Circulatory Physiology

Volume

293

Issue

6

Number of Pages

-

Document Type

Article

Personal Identifier

scopus

DOI Link

https://doi.org/10.1152/ajpheart.00919.2007

Socpus ID

36849008272 (Scopus)

Source API URL

https://api.elsevier.com/content/abstract/scopus_id/36849008272

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