Attenuation of MG132-induced HeLa cell death by N-acetyl cysteine via reducing reactive oxygen species and preventing glutathione depletion.
MG132 as a proteasome inhibitor can induce apoptotic cell death through formation of reactive oxygen species (ROS). In this study, the effects of N-acetyl cysteine (NAC; an antioxidant) on MG132-induced HeLa cell death in relation to ROS and glutathione (GSH) were investigated. MG132 induced cell growth inhibition and apoptosis in HeLa cells, which was accompanied by the loss of mitochondrial membrane potential (MMP; Delta Psi(m)), activation of caspase-3 and poly (ADP-ribose) polymerase (PARP) cleavage. MG132 increased ROS levels, including O(2)(*-), and GSH depleted cell numbers of HeLa cells. NAC reduced the number of annexin V-positive cells and MMP (Delta Psi(m)) loss by MG132. In addition, NAC significantly reduced the ROS level and prevented GSH depletion. In conclusion, NAC prevented MG132-induced HeLa cell death via decreasing ROS and preventing GSH depletion.
Han
Yong Hwan
YH
Department of Physiology, Medical School, Chonbuk National University, JeonJu, Republic of Korea.
Yang
Yeon Mi
YM
Kim
Sung Zoo
SZ
Park
Woo Hyun
WH
D000111:Acetylcysteine / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000502:physiology; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D007976:Leupeptins / Q000494:pharmacology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D061988:Proteasome Inhibitors; D017382:Reactive Oxygen Species / Q000378:metabolism*
D000970:Antineoplastic Agents; D007976:Leupeptins; D061988:Proteasome Inhibitors; D017382:Reactive Oxygen Species; D053148:Caspase 3; D005978:Glutathione; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde; D000111:Acetylcysteine