title: Effects of pharmacological inhibition of AMP-activated protein kinase on GLUT3 expression and the development of ischemic tolerance in astrocytes.
abstract: Ischemic tolerance resulting from preconditioning ischemia is a neuroprotective mechanism. In cultured astrocytes, its development depends on regulation of the expression of glucose transporter 3 (GLUT3) by the stress sensor/effector AMP-activated protein kinase (AMPK). Here we demonstrate that GLUT3 is upregulated during preconditioning and then downregulated during recovery. We also found that, although AMPK inhibition during preconditioning initially suppressed the upregulation of GLUT3 as shown previously, this was followed by a period of GLUT3 upregulation, enhanced glycogen accumulation, and enhanced tolerance to a subsequent ischemic challenge. These results reveal that AMPK has a complex influence on ischemic tolerance.
authors.affiliation: Department of Molecular Physiology & Biophysics, University of Iowa Carver College of Medicine, Iowa City, USA; Laboratory of Cellular Cybernetics, Graduate School of Information Science and Technology, Hokkaido University, Sapporo, Japan. Electronic address: sadahiro-iwabuchi@uiowa.edu.
authors.forename: Sadahiro
authors.initials: S
authors.lastname: Iwabuchi
authors.affiliation: Laboratory of Cellular Cybernetics, Graduate School of Information Science and Technology, Hokkaido University, Sapporo, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Kawahara
authors.affiliation: Department of Molecular Physiology & Biophysics, University of Iowa Carver College of Medicine, Iowa City, USA.
authors.forename: N Charles
authors.initials: NC
authors.lastname: Harata
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000818:Animals; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism*; D002540:Cerebral Cortex / Q000166:cytology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D005947:Glucose / Q000172:deficiency; D051274:Glucose Transporter Type 3 / Q000235:genetics / Q000378:metabolism*; D000860:Hypoxia / Q000473:pathology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D051381:Rats
chemical_list: D051274:Glucose Transporter Type 3; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C495690:Slc2a3 protein, rat; D007770:L-Lactate Dehydrogenase; D055372:AMP-Activated Protein Kinases; D005947:Glucose
keywords: AMPK; Astrocytes; GLUT3; Ischemic tolerance