Effect of middle cerebral artery occlusion on mRNA expression for the sodium-coupled vitamin C transporter SVCT2 in rat brain.
The sodium-vitamin C co-transporter SVCT2 is primarily responsible for the accumulation of the important antioxidant ascorbate into brain cells. In vitro studies have demonstrated strong expression of this transporter in cultured astrocytes, whereas in situ hybridization analysis has so far detected SVCT2 only in neurons. In the present study, we examined the response of SVCT2 mRNA expression in the brain to focal ischemia induced for 2 h by unilateral middle cerebral artery occlusion. The mRNA expression patterns of SVCT2 and the glutamate-activated immediate early gene Arc were investigated at 2 and 22 h after ischemia. SVCT2 and Arc mRNA expression was lost in the ischemic core at both time points. In areas outside the core, Arc was strongly up-regulated, primarily at 2 h, whereas SVCT2 showed an increase at 2 and 22 h. SVCT2 expression was increased in neurons as well as in astrocytes, providing the first evidence for SVCT2 expression in astrocytes in situ. These findings underscore the importance of ascorbate as a neuroprotective agent and may have implications for therapeutic strategies. In addition, the increase of SVCT2 in astrocytes after ischemia suggests that cultured astrocytes are exposed to chronic oxidative stress.
Berger
Urs V
UV
Membrane Biology Program and Renal Division, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Lu
Xi-Chun M
XC
Liu
Weilin
W
Tang
Zhaocheng
Z
Slusher
Barbara S
BS
Hediger
Matthias A
MA
D000818:Animals; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology; D001921:Brain / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology; D003598:Cytoskeletal Proteins; D004195:Disease Models, Animal; D018450:Disease Progression; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism; D017403:In Situ Hybridization; D020244:Infarction, Middle Cerebral Artery / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009419:Nerve Tissue Proteins; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D029363:Organic Anion Transporters, Sodium-Dependent / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D060347:Sodium-Coupled Vitamin C Transporters; D027981:Symporters / Q000235:genetics*
D003598:Cytoskeletal Proteins; D017874:Immediate-Early Proteins; D009419:Nerve Tissue Proteins; D029363:Organic Anion Transporters, Sodium-Dependent; D012333:RNA, Messenger; C555167:Slc23a2 protein, rat; D060347:Sodium-Coupled Vitamin C Transporters; D027981:Symporters; C092069:activity regulated cytoskeletal-associated protein