Research Repository

Overexpression of Human Catalase Inhibits Proliferation and Promotes Apoptosis in Vascular Smooth Muscle Cells

Brown, Michael R and Miller, Francis J and Li, Wei-Gen and Ellingson, Andy N and Mozena, Jonathan D and Chatterjee, Papri and Engelhardt, John F and Zwacka, Ralf M and Oberley, Larry W and Fang, Xiang and Spector, Arthur A and Weintraub, Neal L (1999) 'Overexpression of Human Catalase Inhibits Proliferation and Promotes Apoptosis in Vascular Smooth Muscle Cells.' Circulation Research, 85 (6). pp. 524-533. ISSN 0009-7330

Full text not available from this repository.

Abstract

<jats:p> <jats:italic>Abstract</jats:italic> —The role of reactive oxygen species, such as superoxide anions (O <jats:sub>2</jats:sub> · <jats:sup>−</jats:sup> ) and hydrogen peroxide (H <jats:sub>2</jats:sub> O <jats:sub>2</jats:sub> ), in modulating vascular smooth muscle cell proliferation and viability is controversial. To investigate the role of endogenously produced H <jats:sub>2</jats:sub> O <jats:sub>2</jats:sub> , rat aortic smooth muscle cells were infected with adenoviral vectors containing cDNA for human catalase (Ad <jats:italic>Cat</jats:italic> ) or a control gene, β-galactosidase (Ad <jats:italic>LacZ</jats:italic> ). Infection with Ad <jats:italic>Cat</jats:italic> resulted in dose-dependent increases in intracellular catalase protein, which was predominantly localized to peroxisomes. After infection with 100 multiplicity of infection (MOI) of Ad <jats:italic>Cat</jats:italic> , cellular catalase activity was increased by 50- to 100-fold, and intracellular H <jats:sub>2</jats:sub> O <jats:sub>2</jats:sub> concentration was reduced, as compared with control. Infection with Ad <jats:italic>Cat</jats:italic> reduced [ <jats:sup>3</jats:sup> 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 [Ad <jats:italic>LacZ</jats:italic> ] versus 0.22±0.08 disintegrations per minute per cell [Ad <jats:italic>Cat</jats:italic> ], <jats:italic>P</jats:italic> &lt;0.05). Five days after infection with 100 MOI of Ad <jats:italic>Cat</jats:italic> , cell numbers were reduced as compared with noninfected or Ad <jats:italic>LacZ</jats:italic> -infected cells (157 780±8413 [Ad <jats:italic>Cat</jats:italic> ], <jats:italic>P</jats:italic> &lt;0.05 versus 233 700±3032 [noninfected] or 222 410±5332 [Ad <jats:italic>LacZ</jats:italic> ]). Furthermore, the number of apoptotic cells was increased 5-fold after infection with 100 MOI of Ad <jats:italic>Cat</jats:italic> as compared with control. Infection with Ad <jats:italic>Cat</jats:italic> resulted in induction of cyclooxygenase (COX)–2, and treatment with a COX-2 inhibitor overcame the Ad <jats:italic>Cat</jats:italic> -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 <jats:sub>2</jats:sub> O <jats:sub>2</jats:sub> importantly modulates survival and proliferation of vascular smooth muscle cells. </jats:p>

Item Type: Article
Uncontrolled Keywords: catalase; apoptosis; vascular smooth muscle cell; cell proliferation; hydrogen peroxide
Subjects: R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Divisions: Faculty of Science and Health
Faculty of Science and Health > Life Sciences, School of
SWORD Depositor: Elements
Depositing User: Elements
Date Deposited: 04 Jul 2017 11:15
Last Modified: 18 Aug 2022 11:33
URI: http://repository.essex.ac.uk/id/eprint/8343

Actions (login required)

View Item View Item