title: Superoxide counteracts low-density lipoprotein-induced human aortic smooth muscle cell proliferation.
abstract: Previously, we demonstrated that the level of intracellular O(2)(-) is increased by low-density lipoprotein (LDL) in human aortic smooth muscle cells (HASMCs). The exact role of O(2)(-) in the LDL-induced proliferation of HASMCs, however, has not been determined. In this study, we found that the increase in the concentrations of intracellular O(2)(-) induced by native and oxidized LDL increased SMC-nitric oxide (NO) uptake rate. Moreover, the treatment of HASMCs with diethyldithiocarbamate (DETC), a superoxide dismutase inhibitor, significantly increased NO uptake rate owing to the increase in intracellular O(2)(-) concentrations. Although native and oxidized LDL decreased soluble guanylyl cyclase (sGC) protein content, they still caused a net increase in cyclic GMP production in HASMCs. In addition, when cyclic GMP production was normalized by sGC protein content and NO uptake rate, it was found to be positively dependent on the level of intracellular H(2)O(2). Finally, we simulated cell proliferation stimulated by native and oxidized LDL as a linear function of intracellular O(2)(-) and H(2)O(2) concentrations, demonstrating that O(2)(-) negatively modulated the native and oxidized LDL-stimulated HASMC proliferation through the increase in NO uptake rate.
authors.affiliation: Department of Chemical Engineering, National Chung Cheng University, Chia-Yi 621, Taiwan.
authors.forename: Chi-Chao
authors.initials: CC
authors.lastname: Yin
authors.forename: Tin-Kwang
authors.initials: TK
authors.lastname: Lin
authors.forename: Kuang-Tse
authors.initials: KT
authors.lastname: Huang
mesh_terms: D001011:Aorta / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008077:Lipoproteins, LDL / Q000008:administration & dosage*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D010100:Oxygen / Q000378:metabolism*; D013481:Superoxides / Q000008:administration & dosage*
chemical_list: D008077:Lipoproteins, LDL; D013481:Superoxides; D010100:Oxygen