Involvement of the p38 MAP kinase in Cr(VI)-induced growth arrest and apoptosis.
Hexavalent chromium [Cr(VI)] is a carcinogenic genotoxin commonly found in industry and the environment. DNA damage resulting from Cr(VI) exposure triggers numerous stress responses, including activation of cell cycle checkpoints and initiation of apoptosis. Mechanisms controlling these responses, while extensively studied, have yet to be fully elucidated. Here, we demonstrate that the p38 mitogen-activated protein kinase (MAPK) is activated by Cr(VI) exposure and that inhibition of p38 function using the selective inhibitor SB203580 results in abrogation of S-phase and G2 cell cycle checkpoints in response to Cr(VI). Also, we observe that inhibition of p38 results in decreased cell survival and increased percentage of apoptotic cells following Cr(VI) treatment. Taken together, these results indicate that p38 function is critical for optimal stress response induced by Cr(VI) exposure.
Wakeman
Timothy P
TP
Department of Genetics, and Department of Biochemistry and Molecular Biology, LSU Health Sciences Center, New Orleans, Louisiana, USA.
Wyczechowska
Dorota
D
Xu
Bo
B
D017209:Apoptosis / Q000187:drug effects*; D002274:Carcinogens, Environmental / Q000633:toxicity*; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002857:Chromium / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
D002274:Carcinogens, Environmental; D004791:Enzyme Inhibitors; D007093:Imidazoles; D011725:Pyridines; D002857:Chromium; C074702:chromium hexavalent ion; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580