title: Induction of thioredoxin-interacting protein is mediated by oxidative stress, calcium, and glucose after brain injury in mice.
abstract: 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.
authors.affiliation: Department of Neurosurgery, and Program in Neurosciences, Stanford University School of Medicine, Stanford, CA 94305–5487, USA.
authors.forename: Gab Seok
authors.initials: GS
authors.lastname: Kim
authors.forename: Joo Eun
authors.initials: JE
authors.lastname: Jung
authors.forename: Purnima
authors.initials: P
authors.lastname: Narasimhan
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Sakata
authors.forename: Pak H
authors.initials: PH
authors.lastname: Chan
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis; D001930:Brain Injuries / Q000378:metabolism*; D002545:Brain Ischemia / Q000378:metabolism; D020013:Calcium Signaling / Q000502:physiology*; D002352:Carrier Proteins / Q000096:biosynthesis*; D002478:Cells, Cultured; D005260:Female; D005947:Glucose / Q000502:physiology*; D006943:Hyperglycemia / Q000378:metabolism; D008297:Male; D051379:Mice; D018384:Oxidative Stress / Q000502:physiology*; D011247:Pregnancy; D013879:Thioredoxins / Q000096:biosynthesis*
chemical_list: D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins; C445672:Txnip protein, mouse; D013879:Thioredoxins; D005947:Glucose