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.