title: The effects of exogenous H2O2 on cell death, reactive oxygen species             and glutathione levels in calf pulmonary artery and human umbilical vein endothelial             cells.
abstract: Enhanced oxidative stress contributes to endothelial dysfunction via the apoptotic induction of endothelial cells (ECs). However, the precise molecular mechanisms underlying its important effect remain unclear. Here, we evaluated the effects of exogenous hydrogen peroxide (H(2)O(2)) on cell growth and death in ECs such as calf pulmonary artery endothelial cells (CPAECs) and human umbilical vein endothelial cells (HUVECs) and investigated its mechanism of action in CPAECs. H(2)O(2) inhibited the growth of CPAECs and HUVECs at 24 h with IC50 of approximately 20 and 300 µM, respectively. H(2)O(2) induced cell death in both ECs, which was accompanied by the loss of mitochondrial membrane potential (MMP; ΔΨ(m)). H(2)O(2)-induced CPAEC death occurred via apoptosis, demonstrated by Annexin V-staining cells and Z-VAD (a pan-caspase inhibitor) treatment. H(2)O(2) increased superoxide anion levels in HUVECs but not in CPAECs. Treatment with 30 µM H(2)O(2) significantly decreased the activities of superoxide dismutases and catalase in CPAECs. H(2)O(2) induced glutathione (GSH) depletion in both ECs. Z-VAD and N-acetyl cysteine (NAC; a well-known antioxidant) attenuated apoptotic cell death and GSH depletion in H(2)O(2)-treated CPAECs. In conclusion, H(2)O(2) induced growth inhibition and death in ECs via GSH depletion. HUVECs were relatively resistant to H(2)O(2) compared with CPAECs. H(2)O(2)-induced CPAEC apoptosis required the activation of various caspases.
authors.affiliation: Department of Physiology, Medical School, Research Institute for Endocrine Sciences, Chonbuk National University, Jeonju 561-180, Republic of Korea. parkwh71@chonbuk.ac.kr
authors.forename: Woo Hyun
authors.initials: WH
authors.lastname: Park
mesh_terms: D000818:Animals; D017209:Apoptosis; D020169:Caspases / Q000378:metabolism; D002417:Cattle; D002460:Cell Line; D049109:Cell Proliferation; D042783:Endothelial Cells / Q000166:cytology* / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism*; D053078:Membrane Potential, Mitochondrial; D011651:Pulmonary Artery / Q000166:cytology; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide; D020169:Caspases; D005978:Glutathione