Protection against oxidant-induced apoptosis by mitochondrial thioredoxin in SH-SY5Y neuroblastoma cells

Yan Chen, Min Yu, Dean P. Jones, J. Timothy Greenamyre, Jiyang Cai

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)256-262
Number of pages7
JournalToxicology and Applied Pharmacology
Volume216
Issue number2
DOIs
StatePublished - Oct 15 2006
Externally publishedYes

Fingerprint

tert-Butylhydroperoxide
Thioredoxins
Neuroblastoma
Oxidants
Oxidative stress
Apoptosis
Oxidative Stress
Antioxidants
Calcium Ionophores
Mitochondrial Membrane Potential
Calcimycin
Serine
Oxidation-Reduction
Glutathione
Cultured Cells
Repair
Aging of materials
Membranes
Oxidation
Mutation

Keywords

  • Apoptosis
  • Mitochondria
  • Neurodegeneration
  • Oxidative stress
  • Thioredoxin

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology

Cite this

Protection against oxidant-induced apoptosis by mitochondrial thioredoxin in SH-SY5Y neuroblastoma cells. / Chen, Yan; Yu, Min; Jones, Dean P.; Greenamyre, J. Timothy; Cai, Jiyang.

In: Toxicology and Applied Pharmacology, Vol. 216, No. 2, 15.10.2006, p. 256-262.

Research output: Contribution to journalArticle

Chen, Yan ; Yu, Min ; Jones, Dean P. ; Greenamyre, J. Timothy ; Cai, Jiyang. / Protection against oxidant-induced apoptosis by mitochondrial thioredoxin in SH-SY5Y neuroblastoma cells. In: Toxicology and Applied Pharmacology. 2006 ; Vol. 216, No. 2. pp. 256-262.
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