Reactive oxygen species and glutathione level changes by a proteasome inhibitor, MG132, partially affect calf pulmonary arterial endothelial cell death.
MG132 as a proteasome inhibitor has been shown to induce apoptotic cell death through the formation of reactive oxygen species (ROS). Here, we evaluated the effects of MG132 on the growth of endothelial cells (ECs), especially calf pulmonary artery endothelial cells (CPAECs), in relation to cell death, ROS, and glutathione (GSH) levels. MG132 dose dependently inhibited the growth of CPAEC and human umbilical vein endothelial cells (HUVECs) at 24 hours. MG132 also induced apoptotic cell death in CPAEC, which were accompanied by the loss of mitochondrial membrane potential (MMP; DeltaPsi(m)). MG132 increased ROS levels, including O(2)(*-) in CPAEC, but not in HUVEC. MG132 also dose dependently increased GSH-depleted cells in both ECs. N-acetyl-cysteine (NAC; a well-known antioxidant) reduced ROS levels in MG132-treated CPAEC with the slight prevention of cell death and GSH depletion. Buthionine sulfoximine (BSO; an inhibitor of GSH synthesis) increased ROS levels and decreased GSH levels in MG132-treated CPAEC without the enhancement of cell death. In conclusion, MG132 inhibited the growth of ECs, especially CPAEC. The changes of ROS and GSH levels by MG132 partially affect CPAEC death.
Han
Yong Hwan
YH
Department of Physiology, Medical School, Research Institute of Clinical Medicine, Center for Healthcare Technology Development Chonbuk National University, JeonJu, Republic of Korea.
Kim
Sung Zoo
SZ
Kim
Suhn Hee
SH
Park
Woo Hyun
WH
D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D019328:Buthionine Sulfoximine / Q000494:pharmacology; D002417:Cattle; D018929:Cell Culture Techniques; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism*; D006801:Humans; D007976:Leupeptins / Q000494:pharmacology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D061988:Proteasome Inhibitors; D011651:Pulmonary Artery / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*
D007976:Leupeptins; D061988:Proteasome Inhibitors; D017382:Reactive Oxygen Species; D019328:Buthionine Sulfoximine; D005978:Glutathione; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde; D000111:Acetylcysteine