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Role of reactive oxygen species and MAPKs in vanadate-induced G2/M phase arrest.
Zhang Z; Leonard SS; Huang C; Vallyathan V; Castranova V; Shi X
Free Radic Biol Med 2003 May; 34(10):1333-1342
Cell growth arrest is an important mechanism in maintaining genomic stability and integrity in response to environmental stress. Using the human lung alveolar epithelial cancer cell line A549, we investigated the role of reactive oxygen species (ROS), extracellular signal-regulated protein kinase (ERK), and p38 protein kinase in vanadate-induced cell growth arrest. Exposure of cells to vanadate led to cell growth arrest at the G2/M phase and caused upregulation of p21 and phospho-cdc2 and degradation of cdc25C in a time- and dose-dependent manner. Vanadate stimulated mitogen-activated protein kinases (MAPKs) family members, as determined by the phosphorylation of ERK and p38. PD98059, an inhibitor of ERK, and SB202190, an inhibitor of p38, inhibited vanadate-induced cell growth arrest, upregulation of p21 and cdc2, and degradation of cdc25C. In addition to hydroxyl radical formation, cellular reduction of vanadate generated superoxide radical and hydrogen peroxide (H2O2), as determined by confocal microscopy using specific dyes. Generation of superoxide radical and H2O2 was inhibited by specific antioxidant enzymes, superoxide dismutase (SOD) and catalase, respectively. ROS activate ERK and p38, which in turn upregulate p21 and cdc2 and cause degradation of cdc25C, leading to cell growth arrest at the G2/M phase. Specific ROS affect different MAPK family members and cell growth regulatory proteins with different potencies.
Protein-biochemistry; Proteins; Cell-biology; Cell-growth; Cellular-function; Cellular-reactions; Vanadium-compounds; Cancer; Stress; Lung-cells; Dose-response; Alveolar-cells; Antioxidants; Enzymes
Dr. Xianglin Shi, National Institute for Occupational Safety and Health, Pathology and Physiology Research Branch, 1095 Willowdale Road, Morgantown, WV 26505
Issue of Publication
Free Radical Biology and Medicine
Page last reviewed: March 3, 2021
Content source: National Institute for Occupational Safety and Health Education and Information Division