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Overexpression of human catalase inhibits proliferation and promotes apoptosis in vascular smooth muscle cells

Brown, MR and Miller, FJ and Li, WG and Ellingson, AN and Mozena, JD and Chatterjee, P and Engelhardt, JF and Zwacka, RM and Oberley, LW and Fang, X and Spector, AA and Weintraub, NL (1999) 'Overexpression of human catalase inhibits proliferation and promotes apoptosis in vascular smooth muscle cells.' Circulation Research, 85 (6). 524 - 533. ISSN 0009-7330

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Abstract

The role of reactive oxygen species, such as superoxide anions (O 2 · - ) and hydrogen peroxide (H 2 O 2 ), in modulating vascular smooth muscle cell proliferation and viability is controversial. To investigate the role of endogenously produced H 2 O 2 , rat aortic smooth muscle cells were infected with adenoviral vectors containing cDNA for human catalase (AdCat) or a control gene, β-galactosidase (AdLacZ). Infection with AdCat resulted in dose-dependent increases in intracellular catalase protein, which was predominantly localized to peroxisomes. After infection with 100 multiplicity of infection (MOI) of AdCat, cellular catalase activity was increased by 50- to 100-fold, and intracellular H 2 O 2 concentration was reduced, as compared with control. Infection with AdCat reduced [ 3 H]thymidine uptake, an index of DNA synthesis, in cells maintained in medium supplemented with 2% serum (0.37 ± 0.09 disintegrations per minute per cell [AdLacZ] versus 0.22 ± 0.08 disintegrations per minute per cell [AdCat], P<0.05). Five days after infection with 100 MOI of AdCat, cell numbers were reduced as compared with noninfected or AdLacZ-infected cells (157 780 ± 8413 [AdCat], P<0.05 versus 233 700 ± 3032 [noninfected] or 222 410 ± 5332 [AdLacZ]). Furthermore, the number of apoptotic cells was increased 5-fold after infection with 100 MOI of AdCat as compared with control. Infection with AdCat resulted in induction of cyclooxygenase (COX)-2, and treatment with a COX-2 inhibitor overcame the AdCat-induced reduction in cell numbers. These findings indicate that overexpression of catalase inhibited smooth muscle proliferation while increasing the rate of apoptosis, possibly through a COX-2-dependent mechanism. Our results suggest that endogenously produced H 2 O 2 importantly modulates survival and proliferation of vascular smooth muscle cells.

Item Type: Article
Subjects: R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Divisions: Faculty of Science and Health > Biological Sciences, School of
Depositing User: Jim Jamieson
Date Deposited: 04 Jul 2017 11:15
Last Modified: 27 Feb 2019 11:15
URI: http://repository.essex.ac.uk/id/eprint/8343

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