Increased mitochondrial thioredoxin 2 potentiates N-ethylmaleimide-induced cytotoxicity

Yan Chen, Young Mi Go, Jan Pohl, Matthew Reed, Jiyang Cai, Dean P. Jones

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Thioredoxin 2 (Trx2) is a mitochondrially localized antioxidant and antiapoptotic protein, whose functions are mainly dependent on the conserved cysteines at its redox active center. In the current study, we showed by mass spectrometry that a thiol alkylating agent, N-ethylmaleimide (NEM), alkylated a single cysteine residue in the active center of Trx2. The interaction between NEM and Trx2 in intact cells was confirmed by redox Western analysis. Overexpression of Trx2 in cultured 143B osteosarcoma cells caused increased sensitivity to NEM. Covalent modification by NEM resulted in a dominant-negative effect and increased the interaction between Trx2 and peroxiredoxin 3 (Prx3). Our data suggest that the alkylation of the essential thiol(s) of Trx2 has profound impact on the mitochondrial redox circuitry and that such effects are distinct from the responses to agents causing reversible disulfide bond formation between the vicinal dithiols in the active center.

Original languageEnglish (US)
Pages (from-to)1205-1210
Number of pages6
JournalChemical Research in Toxicology
Volume21
Issue number6
DOIs
StatePublished - Jun 2008
Externally publishedYes

Fingerprint

Thioredoxins
Ethylmaleimide
Cytotoxicity
Oxidation-Reduction
Sulfhydryl Compounds
Cysteine
Peroxiredoxin III
Alkylating Agents
Alkylation
Osteosarcoma
Disulfides
Mass spectrometry
Mass Spectrometry
Antioxidants
Proteins

ASJC Scopus subject areas

  • Drug Discovery
  • Organic Chemistry
  • Chemistry(all)
  • Toxicology
  • Health, Toxicology and Mutagenesis

Cite this

Increased mitochondrial thioredoxin 2 potentiates N-ethylmaleimide-induced cytotoxicity. / Chen, Yan; Go, Young Mi; Pohl, Jan; Reed, Matthew; Cai, Jiyang; Jones, Dean P.

In: Chemical Research in Toxicology, Vol. 21, No. 6, 06.2008, p. 1205-1210.

Research output: Contribution to journalArticle

Chen, Yan ; Go, Young Mi ; Pohl, Jan ; Reed, Matthew ; Cai, Jiyang ; Jones, Dean P. / Increased mitochondrial thioredoxin 2 potentiates N-ethylmaleimide-induced cytotoxicity. In: Chemical Research in Toxicology. 2008 ; Vol. 21, No. 6. pp. 1205-1210.
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