Induction of thioredoxin-interacting protein is mediated by oxidative stress, calcium, and glucose after brain injury in mice

Gab Seok Kim, Joo Eun Jung, Purnima Narasimhan, Hiroyuki Sakata, Pak H. Chan

Research output: Contribution to journalArticlepeer-review

51 Citations (Scopus)


Oxidative stress and glucose affect the expression of various genes that contribute to both reactive oxygen species generation and antioxidant systems. However, systemic alteration of oxidative stress-related gene expression in normal brains and in brains with a high-glucose status after ischemic-reperfusion has not been explored. Using a polymerase chain reaction array system, we demonstrate that thioredoxin-interacting protein (Txnip) is induced by both oxidative stress and glucose. We found that Txnip mRNA is induced by ischemic-reperfusion injury and that Txnip is located in the cytoplasm of neurons. Moreover, in vitro oxygen-glucose deprivation (OGD) and subsequent reoxygenation without glucose and in vivo administration of 3-nitropropionic acid also promoted an increase in Txnip in a time-dependent manner, indicating that oxidative stress without glucose can induce Txnip expression in the brain. However, calcium channel blockers inhibit induction of Txnip after OGD and reoxygenation. Using the polymerase chain reaction array with ischemic and hyperglycemic-ischemic samples, we confirmed that enhanced expression of Txnip was observed in hyperglycemic-ischemic brains after middle cerebral artery occlusion. Finally, transfection of Txnip small interfering RNA into primary neurons reduced lactate dehydrogenase release after OGD and reoxygenation. This is the first report showing that Txnip expression is induced in neurons after oxidative or glucose stress under either ischemic or hyperglycemic-ischemic conditions, and that Txnip is proapoptotic under these conditions.

Original languageEnglish
Pages (from-to)440-449
Number of pages10
JournalNeurobiology of Disease
Issue number2
Publication statusPublished - 2012 May
Externally publishedYes


  • Middle cerebral artery occlusion
  • Oxygen-glucose deprivation
  • Polymerase chain reaction array
  • Reactive oxygen species
  • Thioredoxin
  • Thioredoxin-interacting protein

ASJC Scopus subject areas

  • Neurology


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