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Superoxide dismutase and catalase inhibit oxidized low-density lipoprotein-induced human aortic smooth muscle cell proliferation: role of cell-cycle regulation, mitogen-activated protein kinases, and transcription factors.
Atherosclerosis. 2007 Jan; 190(1):124-34.A

Abstract

Several antioxidant enzymes, including copper, zinc-superoxide dismutase (Cu, Zn-SOD) and catalase, have been suggested to be protective against the proliferation of vascular smooth muscle cells exposed to oxidative stress. In the present study, we investigated effects of Cu, Zn-SOD and/or catalase on oxLDL-induced proliferation of, and intracellular signaling in, human aortic smooth muscle cells (HASMCs). HASMCs were transfected with adenovirus carrying the human Cu, Zn-SOD gene and/or the human catalase gene. This resulted in a high level of Cu, Zn-SOD and/or catalase overexpression and decreased oxLDL-induced proliferation. Cu, Zn-SOD and/or catalase also arrested cell cycle progression, which was associated with decreased expression of cyclin D1, cyclin E, CDK2, and CDK4 and upregulation of p21(Cip1) and p27(Kip1). Phosphorylation studies on ERK1/2, JNK, and p38, three major subgroups of mitogen activator protein kinases, demonstrated that Cu, Zn-SOD and/or catalase overexpression suppressed ERK1/2 and JNK phosphorylation. Gel-mobility shift analysis showed that oxLDL caused an increase in the DNA binding activity of activator protein-1 (AP-1) and nuclear factor kappaB (NF-kappaB), which was inhibited by Cu, Zn-SOD and/or catalase overexpression. These results provide the first evidence that overexpression of Cu, Zn-SOD and/or catalase in HASMCs attenuates the cell proliferation caused by oxLDL stimulation and that this inhibitory effect is mediated via downregulation of ERK1/2 and JNK phosphorylation and AP-1 and NF-kappaB inactivation. These observations support the feasibility of the increase of Cu, Zn-SOD and/or catalase expression in human smooth muscle cells as a means of protection against oxidant injury.

Authors+Show Affiliations

Institute of Clinical Medicine, National Yang-Ming University, Taiwan, Republic of China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16600249

Citation

Lin, Shing-Jong, et al. "Superoxide Dismutase and Catalase Inhibit Oxidized Low-density Lipoprotein-induced Human Aortic Smooth Muscle Cell Proliferation: Role of Cell-cycle Regulation, Mitogen-activated Protein Kinases, and Transcription Factors." Atherosclerosis, vol. 190, no. 1, 2007, pp. 124-34.
Lin SJ, Shyue SK, Shih MC, et al. Superoxide dismutase and catalase inhibit oxidized low-density lipoprotein-induced human aortic smooth muscle cell proliferation: role of cell-cycle regulation, mitogen-activated protein kinases, and transcription factors. Atherosclerosis. 2007;190(1):124-34.
Lin, S. J., Shyue, S. K., Shih, M. C., Chu, T. H., Chen, Y. H., Ku, H. H., Chen, J. W., Tam, K. B., & Chen, Y. L. (2007). Superoxide dismutase and catalase inhibit oxidized low-density lipoprotein-induced human aortic smooth muscle cell proliferation: role of cell-cycle regulation, mitogen-activated protein kinases, and transcription factors. Atherosclerosis, 190(1), 124-34.
Lin SJ, et al. Superoxide Dismutase and Catalase Inhibit Oxidized Low-density Lipoprotein-induced Human Aortic Smooth Muscle Cell Proliferation: Role of Cell-cycle Regulation, Mitogen-activated Protein Kinases, and Transcription Factors. Atherosclerosis. 2007;190(1):124-34. PubMed PMID: 16600249.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Superoxide dismutase and catalase inhibit oxidized low-density lipoprotein-induced human aortic smooth muscle cell proliferation: role of cell-cycle regulation, mitogen-activated protein kinases, and transcription factors. AU - Lin,Shing-Jong, AU - Shyue,Song-Kun, AU - Shih,Meng-Chun, AU - Chu,Ting-Hui, AU - Chen,Yung-Hsiang, AU - Ku,Hung-Hai, AU - Chen,Jaw-Wen, AU - Tam,Ka-Bik, AU - Chen,Yuh-Lien, Y1 - 2006/04/05/ PY - 2005/08/26/received PY - 2006/02/13/revised PY - 2006/02/20/accepted PY - 2006/4/8/pubmed PY - 2007/3/22/medline PY - 2006/4/8/entrez SP - 124 EP - 34 JF - Atherosclerosis JO - Atherosclerosis VL - 190 IS - 1 N2 - Several antioxidant enzymes, including copper, zinc-superoxide dismutase (Cu, Zn-SOD) and catalase, have been suggested to be protective against the proliferation of vascular smooth muscle cells exposed to oxidative stress. In the present study, we investigated effects of Cu, Zn-SOD and/or catalase on oxLDL-induced proliferation of, and intracellular signaling in, human aortic smooth muscle cells (HASMCs). HASMCs were transfected with adenovirus carrying the human Cu, Zn-SOD gene and/or the human catalase gene. This resulted in a high level of Cu, Zn-SOD and/or catalase overexpression and decreased oxLDL-induced proliferation. Cu, Zn-SOD and/or catalase also arrested cell cycle progression, which was associated with decreased expression of cyclin D1, cyclin E, CDK2, and CDK4 and upregulation of p21(Cip1) and p27(Kip1). Phosphorylation studies on ERK1/2, JNK, and p38, three major subgroups of mitogen activator protein kinases, demonstrated that Cu, Zn-SOD and/or catalase overexpression suppressed ERK1/2 and JNK phosphorylation. Gel-mobility shift analysis showed that oxLDL caused an increase in the DNA binding activity of activator protein-1 (AP-1) and nuclear factor kappaB (NF-kappaB), which was inhibited by Cu, Zn-SOD and/or catalase overexpression. These results provide the first evidence that overexpression of Cu, Zn-SOD and/or catalase in HASMCs attenuates the cell proliferation caused by oxLDL stimulation and that this inhibitory effect is mediated via downregulation of ERK1/2 and JNK phosphorylation and AP-1 and NF-kappaB inactivation. These observations support the feasibility of the increase of Cu, Zn-SOD and/or catalase expression in human smooth muscle cells as a means of protection against oxidant injury. SN - 0021-9150 UR - https://www.unboundmedicine.com/medline/citation/16600249/Superoxide_dismutase_and_catalase_inhibit_oxidized_low_density_lipoprotein_induced_human_aortic_smooth_muscle_cell_proliferation:_role_of_cell_cycle_regulation_mitogen_activated_protein_kinases_and_transcription_factors_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0021-9150(06)00117-1 DB - PRIME DP - Unbound Medicine ER -