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

Michael R. Brown, Francis J. Miller, Wei Gen Li, Andy N. Ellingson, Jonathan D. Mozena, Papri Chatterjee, John F. Engelhardt, Ralf M. Zwacka, Larry W. Oberley, Xiang Fang, Arthur A. Spector, Neal L. Weintraub

Research output: Contribution to journalArticle

173 Scopus citations

Abstract

The role of reactive oxygen species, such as superoxide anions (O2·-) and hydrogen peroxide (H2O2), in modulating vascular smooth muscle cell proliferation and viability is controversial. To investigate the role of endogenously produced H2O2, 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 H2O2 concentration was reduced, as compared with control. Infection with AdCat reduced [3H]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 H2O2 importantly modulates survival and proliferation of vascular smooth muscle cells.

Original languageEnglish (US)
Pages (from-to)524-533
Number of pages10
JournalCirculation Research
Volume85
Issue number6
DOIs
StatePublished - Sep 17 1999
Externally publishedYes

Keywords

  • Apoptosis
  • Catalase
  • Cell proliferation
  • Hydrogen peroxide
  • Vascular smooth muscle cell

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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    Brown, M. R., Miller, F. J., Li, W. G., Ellingson, A. N., Mozena, J. D., Chatterjee, P., Engelhardt, J. F., Zwacka, R. M., Oberley, L. W., Fang, X., Spector, A. A., & Weintraub, N. L. (1999). Overexpression of human catalase inhibits proliferation and promotes apoptosis in vascular smooth muscle cells. Circulation Research, 85(6), 524-533. https://doi.org/10.1161/01.RES.85.6.524