Protection against oxidant-induced apoptosis by mitochondrial thioredoxin in SH-SY5Y neuroblastoma cells
- Vanderbilt Eye Institute, Vanderbilt University Medical Center, Nashville, TN 37232 (United States)
- Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, Atlanta, GA 30322 (United States)
- Center of Neurodegenerative Disease, Emory University School of Medicine, Atlanta, GA 30322 (United States)
- Vanderbilt Eye Institute, Vanderbilt University Medical Center, Nashville, TN 37232 (United States) and Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, Atlanta, GA 30322 (United States)
Mitochondrial oxidative stress plays important roles in aging and age-related degenerative disorders. The newly identified mitochondrial thioredoxin (mtTrx; Trx2) is a key component of the mitochondrial antioxidant system which is responsible for the clearance of reactive intermediates and repairs proteins with oxidative damage. Here, we show that in cultured SH-SY5Y human neuroblastoma 1cells, overexpression of mtTrx inhibited apoptosis and loss of mitochondrial membrane potential induced by a chemical oxidant, tert-butylhydroperoxide (tBH). The effects of calcium ionophore (Br-A23187) were not affected by mtTrx, suggesting the protection was specific against oxidative injury. The mitochondrial glutathione pool was oxidized by tBH, and this oxidation was not inhibited by increased mtTrx. Consequently, the antioxidant function of mtTrx is not redundant, but rather in addition, to that of GSH. Mutations of Cys90 and Cys93 to serines rendered mtTrx ineffective in protection against tBH-induced cytoxicity. These data indicate that mtTrx controls the mitochondrial redox status independently of GSH and is a key component of the defensive mechanism against oxidative stress in cultured neuronal cells.
- OSTI ID:
- 20850446
- Journal Information:
- Toxicology and Applied Pharmacology, Vol. 216, Issue 2; Other Information: DOI: 10.1016/j.taap.2006.05.006; PII: S0041-008X(06)00174-8; Copyright (c) 2006 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0041-008X
- Country of Publication:
- United States
- Language:
- English
Similar Records
Enhanced oxidative stress and aberrant mitochondrial biogenesis in human neuroblastoma SH-SY5Y cells during methamphetamine induced apoptosis
Survivin knockdown increased anti-cancer effects of (-)-epigallocatechin-3-gallate in human malignant neuroblastoma SK-N-BE2 and SH-SY5Y cells