The effects of MAPK inhibitors on a proteasome inhibitor, MG132-induced HeLa cell death in relation to reactive oxygen species and glutathione.
MG132 as a proteasome inhibitor can induce apoptotic cell death through formation of reactive oxygen species (ROS). In this study, we investigated the effects of MAPK (MEK, JNK or p38) inhibitors on MG132-induced HeLa cell death in relation to ROS and glutathione (GSH). MG132-induced cell growth inhibition and apoptosis in HeLa cells, which was accompanied by the loss of mitochondrial membrane potential (MMP; DeltaPsi(m)). MG132 increased ROS level including O(2)(*-) and GSH depleted cell number in HeLa cells. All the MAPK inhibitors slightly enhanced the cell growth inhibition but did not intensify apoptosis in MG132-treated HeLa cells. Each MAPK inhibitor differentially changed the levels of ROS and GSH content in MG132-treated cells. In conclusion, MAPK inhibitors partially influence apoptosis, ROS and GSH levels in MG132-treated HeLa cells.
Han
Yong Hwan
YH
Department of Physiology, Medical School, Institute for Medical Sciences, Chonbuk National University, Deokjin-gu, JeonJu, Republic of Korea.
Park
Woo Hyun
WH
D017209:Apoptosis / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D004347:Drug Interactions; D005978:Glutathione / Q000378:metabolism*; D006131:Growth Inhibitors / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D007976:Leupeptins / Q000494:pharmacology*; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors*; D011480:Protease Inhibitors / Q000494:pharmacology*; D061988:Proteasome Inhibitors; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism*
D006131:Growth Inhibitors; D007976:Leupeptins; D011480:Protease Inhibitors; D061988:Proteasome Inhibitors; D047428:Protein Kinase Inhibitors; D017382:Reactive Oxygen Species; D020928:Mitogen-Activated Protein Kinases; D005978:Glutathione; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde