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. DOI https://doi.org/10.1161/01.res.85.6.524
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. DOI https://doi.org/10.1161/01.res.85.6.524
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. DOI https://doi.org/10.1161/01.res.85.6.524
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><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><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 |
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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: | Unnamed user with email elements@essex.ac.uk |
Depositing User: | Unnamed user with email elements@essex.ac.uk |
Date Deposited: | 04 Jul 2017 11:15 |
Last Modified: | 04 Jul 2023 02:55 |
URI: | http://repository.essex.ac.uk/id/eprint/8343 |