p38 and ERK1/2 MAPKs mediate the interplay of TNF-alpha and IL-10 in regulating oxidative stress and cardiac myocyte apoptosis
Abbreviated Journal Title
Am. J. Physiol.-Heart Circul. Physiol.
cell communication; heart failure; mitogen-activated protein kinase; signal transduction; NECROSIS-FACTOR-ALPHA; HEART-FAILURE; CARDIOMYOCYTE APOPTOSIS; PROTEIN-KINASES; CELL-DEATH; INJURY; EXPRESSION; SURVIVAL; PATHWAY; INTERLEUKIN-10; Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular; Disease
It is known that TNF-alpha 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-alpha and IL-10 in regulating oxidative stress and cardiac myocyte apoptosis in Sprague-Dawley male rats. Isolated adult cardiac myocytes were exposed to TNF-alpha (10 ng/ml), IL-10 (10 ng/ml), and IL-10 + TNF-alpha (ratio 1) for 4 h. H2O2 (100 mu M) as a positive control and the antioxidant Trolox (20 mu mol/l) were used to confirm the involvement of oxidative stress. H2O2 treatment increased oxidative stress and apoptosis; TNF-alpha mimicked these effects. Exposure to TNF-alpha 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-alpha. The antioxidant Trolox modulated TNF-alpha-induced changes in Bax/Bcl-xl, cell injury, and MAPKs. Preexposure of cells to the p38 MAPK inhibitor SB-203580 prevented TNF-alpha-induced changes. Inhibition of the ERK pathway with PD-98059 attenuated the protective role of IL-10 against TNF-alpha-induced apoptosis. This study provides evidence in support of the essential role of p38 and ERK1/2 MAPKs in the interactive role of TNF-alpha and IL-10 in cardiac myocyte apoptosis.
American Journal of Physiology-Heart and Circulatory Physiology
"p38 and ERK1/2 MAPKs mediate the interplay of TNF-alpha and IL-10 in regulating oxidative stress and cardiac myocyte apoptosis" (2007). Faculty Bibliography 2000s. 7029.