|
|
||||||||
Departments of 1 Cell Biology and Neuroscience and 2 Pharmacology, College of Medicine, University of South Alabama, Mobile, Alabama 36688; and 3 Wells Center for Pediatric Research, Indiana University Medical School, Indianapolis, Indiana 46202
In rat cultured pulmonary arterial (PA), microvascular, and venous endothelial cells (ECs), the rate of mitochondrial (mt) DNA repair is predictive of the severity of xanthine oxidase (XO)-induced mtDNA damage and the sensitivity to XO-mediated cell death. To examine the importance of mtDNA damage and repair more directly, we determined the impact of mitochondrial overexpression of the DNA repair enzyme, Ogg1, on XO-induced mtDNA damage and cell death in PAECs. PAECs were transiently transfected with an Ogg1-mitochondrial targeting sequence construct. Mitochondria-selective overexpression of the transgene product was confirmed microscopically by the observation that immunoreactive Ogg1 colocalized with a mitochondria-specific tracer and, with an oligonucleotide cleavage assay, by a selective enhancement of mitochondrial Ogg1 activity. Overexpression of Ogg1 protected against both XO-induced mtDNA damage, determined by quantitative Southern analysis, and cell death as assessed by trypan blue exclusion and MTS assays. These findings show that mtDNA damage is a direct cause of cell death in XO-treated PAECs.
mitochondrial deoxyribonucleic acid; xanthine oxidase; Ogg1; cytotoxicity
This article has been cited by other articles:
![]() |
S. Zhong, Z. Li, L. Huan, and B.-Y. Chen Neurochemical Mechanism of Electroacupuncture: Anti-injury Effect on Cerebral Function after Focal Cerebral Ischemia in Rats Evid. Based Complement. Altern. Med., March 1, 2009; 6(1): 51 - 56. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. A. Klimova, E. L. Bell, E. H. Shroff, F. D. Weinberg, C. M. Snyder, G. P. Dimri, P. T. Schumacker, G. R. S. Budinger, and N. S. Chandel Hyperoxia-induced premature senescence requires p53 and pRb, but not mitochondrial matrix ROS FASEB J, March 1, 2009; 23(3): 783 - 794. [Abstract] [Full Text] [PDF] |
||||
![]() |
L. Xie, X. Zhu, Y. Hu, T. Li, Y. Gao, Y. Shi, and S. Tang Mitochondrial DNA Oxidative Damage Triggering Mitochondrial Dysfunction and Apoptosis in High Glucose-Induced HRECs Invest. Ophthalmol. Vis. Sci., September 1, 2008; 49(9): 4203 - 4209. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Cai, Y. Xu, R. J. Cooper, M. J. Ferkowicz, J. R. Hartwell, K. E. Pollok, and M. R. Kelley Mitochondrial Targeting of Human O6-Methylguanine DNA Methyltransferase Protects against Cell Killing by Chemotherapeutic Alkylating Agents Cancer Res., April 15, 2005; 65(8): 3319 - 3327. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Ruchko, O. Gorodnya, S. P. LeDoux, M. F. Alexeyev, A.-B. Al-Mehdi, and M. N. Gillespie Mitochondrial DNA damage triggers mitochondrial dysfunction and apoptosis in oxidant-challenged lung endothelial cells Am J Physiol Lung Cell Mol Physiol, March 1, 2005; 288(3): L530 - L535. [Abstract] [Full Text] [PDF] |
||||
![]() |
L. I. Rachek, V. I. Grishko, M. F. Alexeyev, V. V. Pastukh, S. P. LeDoux, and G. L. Wilson Endonuclease III and endonuclease VIII conditionally targeted into mitochondria enhance mitochondrial DNA repair and cell survival following oxidative stress Nucleic Acids Res., June 15, 2004; 32(10): 3240 - 3247. [Abstract] [Full Text] [PDF] |
||||
![]() |
V. Panduri, S. A. Weitzman, N. S. Chandel, and D. W. Kamp Mitochondrial-derived free radicals mediate asbestos-induced alveolar epithelial cell apoptosis Am J Physiol Lung Cell Mol Physiol, June 1, 2004; 286(6): L1220 - L1227. [Abstract] [Full Text] [PDF] |
||||
![]() |
M.-R. Lee, S.-H. Kim, H.-J. Cho, K.-Y. Lee, A. R. Moon, H. G. Jeong, J.-S. Lee, J.-W. Hyun, M.-H. Chung, and H. J. You Transcription Factors NF-YA Regulate the Induction of Human OGG1 Following DNA-alkylating Agent Methylmethane Sulfonate (MMS) Treatment J. Biol. Chem., March 12, 2004; 279(11): 9857 - 9866. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. T. Lightfoot, S. Khov, and H. Ischiropoulos Transient injury to rat lung mitochondrial DNA after exposure to hyperoxia and inhaled nitric oxide Am J Physiol Lung Cell Mol Physiol, January 1, 2004; 286(1): L23 - L29. [Abstract] [Full Text] [PDF] |
||||
![]() |
L. I. Rachek, V. I. Grishko, S. I. Musiyenko, M. R. Kelley, S. P. LeDoux, and G. L. Wilson Conditional Targeting of the DNA Repair Enzyme hOGG1 into Mitochondria J. Biol. Chem., November 15, 2002; 277(47): 44932 - 44937. [Abstract] [Full Text] [PDF] |
||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |