title: Exogenous H2O2 induces growth inhibition and cell death of human pulmonary artery smooth muscle cells via glutathione depletion.
abstract: Reactive oxygen species (ROS) are associated with various pathophysiological processes of vascular smooth muscle cells (VSMCs). Pyrogallol (PG) induces the superoxide anion (O2•‑)‑mediated cell death of numerous cell types. The present study aimed to investigate the effects of exogenous hydrogen peroxide (H2O2) and PG treatment on the cell growth and death of human pulmonary artery smooth muscle cells (HPASMCs), with regards to intracellular ROS and glutathione (GSH) levels, as determined by MTT and cell number assays. H2O2 led to reduced growth of HPASMCs, with a half maximal inhibitory concentration of 250‑500 µM at 24 h, and induced apoptosis, as determined by Annexin V‑staining and benzyloxycarbonyl‑Val‑Ala‑Asp‑fluoromethylketone treatment. However, PG did not strongly induce growth inhibition and death of HPASMCs. In addition, H2O2 led to increased ROS levels, including mitochondrial O2•‑, and induced GSH depletion in HPASMCs. Treatment with N‑acetyl cysteine (NAC) attenuated apoptotic cell death and ROS levels in H2O2‑treated HPASMCs, and also prevented GSH depletion. Notably, PG treatment did not increase ROS levels, including mitochondrial O2•‑. Furthermore, NAC induced a significant increase in mitochondrial O2•‑ levels in PG‑treated HPASMCs, and cell death and GSH depletion were significantly increased. L‑buthionine sulfoximine intensified cell death and GSH depletion in PG‑treated HPASMCs. In conclusion, exogenous H2O2 induced growth inhibition and cell death of HPASMCs via GSH depletion.
authors.affiliation: Department of Physiology, Medical School, Research Institute for Endocrine Sciences, Chonbuk National University, Jeonju, North Jeolla 561‑180, Republic of Korea.
authors.forename: Woo Hyun
authors.initials: WH
authors.lastname: Park
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005978:Glutathione / Q000378:metabolism*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D042541:Intracellular Space; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000378:metabolism*; D010084:Oxidation-Reduction / Q000187:drug effects; D011651:Pulmonary Artery / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide; D005978:Glutathione