MG132, a proteasome inhibitor, induced death of calf pulmonary artery endothelial cells via caspase-dependent apoptosis and GSH depletion.
MG132, a proteasome inhibitor, has been shown to induce apoptotic cell death through formation of reactive oxygen species (ROS). Here, we evaluated the effects of MG132 on the growth of endothelial cells, especially calf pulmonary artery endothelial cells (CPAECs). MG132 dose-dependently inhibited the growth of CPAECSs and human umbilical vein endothelial cells (HUVECs) at 24 hours. MG132 also induced apoptosis in both cell lines, which was accompanied by the loss of mitochondrial membrane potential. All the tested caspase inhibitors (pan-caspase, caspase-3, -8 and -9 inhibitor) significantly rescued CPAECs from MG132-induced cell death. MG132 increased ROS level and GSH depleted cell numbers of CPAECs. None of the caspase inhibitors reduced ROS level in MG132-treated CPAECs but did reduce apoptosis in these cells. In conclusion, MG132 inhibited the growth of endothelial cells, especially CPAECs via caspase-dependent apoptosis. MG132-induced CPAEC death was related to GSH depletion rather than a change in ROS level.
Han
Yong Hwan
YH
Associate Professor, Department of Physiology, Medical School Chonbuk National University, JeonJu, Republic of Korea.
Moon
Hwa Jin
HJ
You
Bo Ra
BR
Yang
Yeon Mi
YM
Kim
Sung Zoo
SZ
Kim
Suhn Hee
SH
Park
Woo Hyun
WH
D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism*; D002417:Cattle; D048708:Cell Growth Processes / Q000187:drug effects; D002460:Cell Line; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D007976:Leupeptins / Q000494:pharmacology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D011651:Pulmonary Artery / Q000166:cytology; D017382:Reactive Oxygen Species / Q000378:metabolism; D014471:Umbilical Veins / Q000166:cytology
D061945:Caspase Inhibitors; D015853:Cysteine Proteinase Inhibitors; D007976:Leupeptins; D017382:Reactive Oxygen Species; D020169:Caspases; D005978:Glutathione; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde