H(2)O(2) regulates cardiac myocyte phenotype via concentration-dependent activation of distinct kinase pathways.

Kwon SH, Pimentel DR, Remondino A, Sawyer DB, Colucci WS
J Mol Cell Cardiol. 2003 35 (6): 615-21

PMID: 12788379 · DOI:10.1016/s0022-2828(03)00084-1

Reactive oxygen species (ROS) can act as signaling molecules to stimulate either hypertrophy or apoptosis in cardiac myocytes. We tested the hypothesis that the phenotypic effects of ROS are due to differential, concentration-dependent activation of specific kinase signaling pathways. Adult rat ventricular myocytes were exposed to H(2)O(2) over a broad concentration range (10-1000 microM). Low concentrations of H(2)O(2) (10-30 microM) increased protein synthesis without affecting survival. Higher concentrations of H(2)O(2) (100-200 microM) increased apoptosis (assessed by TUNEL). Still higher concentrations of H(2)O(2) (300-1000 microM) caused both apoptosis and necrosis. A hypertrophic concentration of H(2)O(2) (10 microM) increased the activity of ERK1/2, but not that of JNK, p38 kinase or Akt. An apoptotic concentration of H(2)O(2) (100 microM) activated JNK, p38 kinase and Akt, and further activated ERK1/2. The MEK1/2 inhibitor U0126 prevented the hypertrophic effect of 10 microM H(2)O(2). The apoptotic effect of 100 microM H(2)O(2) was inhibited bya dominant-negative JNK adenovirus, and was potentiated by U0126 or an Akt inhibitor. Thus, the concentration-dependent effects of ROS on myocyte hypertrophy and growth are due, at least in part, to the differential activation of specific kinase signaling pathways that regulate hypertrophy and apoptosis.

MeSH Terms (22)

Adenoviridae Animals Apoptosis Blotting, Western Cell Survival Dose-Response Relationship, Drug Hydrogen Peroxide In Situ Nick-End Labeling Leucine Male Mitogen-Activated Protein Kinase 1 Mitogen-Activated Protein Kinase 3 Mitogen-Activated Protein Kinases Muscle Cells Myocardium Necrosis p38 Mitogen-Activated Protein Kinases Phenotype Rats Rats, Sprague-Dawley Reactive Oxygen Species Signal Transduction

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