Overexpression of thioredoxin-binding protein 2increases oxidation sensitivity and apoptosis in human lens epithelialcells

Yibo Yu, Kuiyi Xing, Rilwan Badamas, Charles A. Kuszynski, Hongli Wu, Marjorie F. Lou

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

Thioredoxin (Trx) is an important redox regulator with cytosolic Trx1 and mitochondrial Trx2 isozymes. Trx has multiple physiological functions in cells and its bioavailability is negatively controlled through active-site binding to a specific thioredoxin-binding protein (TBP-2). This paper describes the delicate balance between TBP-2 and Trx and the effect of overexpression of TBP-2 in human lens epithelial cells. Cells overexpressing TBP-2 (TBP-2 OE) showed a sevenfold increase in TBP-2 and a nearly 40% suppression of Trx activity but no change in Trx expression. The TBP-2 OE cells grew slower and their population decreased to 30% by day 7. Cell cycle analysis showed that TBP-2 OE cells arrested at the G2/M stage and that they displayed low expression of the cell cycle elements P-cdc2(Y15), cdc2, cdc25A, and cdc25C. Furthermore, TBP-2 OE cells were more sensitive to oxidation. Under H2O2 (200 μM, 24 h) treatment, these cells lost 80% viability and became highly apoptotic. Brief oxidative stress (200 μM, 30 min) to TBP-2 OE cells disrupted the Trx antiapoptotic function by dissociating the cytosolic and mitochondrial Trx-ASK binding complexes. The same H2O 2-treated cells also showed activated ASK (P-ASK), increased Bax, lowered Bcl-2, cytochrome c release, and elevated caspase 3/7 activity. We conclude from these studies that high cellular levels of TBP-2 can potentially suppress Trx bioavailability and increase oxidation sensitivity. Overexpression of TBP-2 also causes slow growth by mitotic arrest and apoptosis by activating the ASK death pathway.

Original languageEnglish
Pages (from-to)92-104
Number of pages13
JournalFree Radical Biology and Medicine
Volume57
DOIs
StatePublished - Apr 2013

Keywords

  • Apoptosis
  • Cell cycle
  • Free radicals
  • Oxidative stress
  • Thioredoxin
  • Thioredoxin-binding protein 2

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