An adenoviral vector expressing the glucose transporter protects cultured striatal neurons from 3-nitropropionic acid.
Considerable interest has focused on the possibility of using gene transfer techniques to introduce protective genes into neurons around the time of necrotic insults. We have previously used herpes simplex virus amplicon vectors to overexpress the rat brain glucose transporter, Glut-1 (GT), and have shown it to protect against a variety of necrotic insults both in vitro and in vivo, as well as to buffer neurons from the steps thought to mediate necrotic injury. It is critical to show the specificity of the effects of any such transgene overexpression, in order to show that protection arises from the transgene delivered, rather than from the vector delivery system itself. As such, we tested the protective potential of GT overexpression driven, in this case, by an adenoviral vector, against a novel insult, namely exposure of primary striatal cultures to the metabolic poison, 3-nitropropionic acid (3NP). We observed that GT overexpression buffered neurons from neurotoxicity induced by 3NP.
Fink
S L
SL
Department of Biological Sciences, Stanford University, Stanford, CA 95406, USA.
Ho
D Y
DY
McLaughlin
J
J
Sapolsky
R M
RM
D000256:Adenoviridae; D000818:Animals; D018929:Cell Culture Techniques; D003292:Convulsants / Q000633:toxicity*; D003342:Corpus Striatum / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D005333:Fetus; D015967:Gene Expression Regulation, Viral; D005822:Genetic Vectors; D051272:Glucose Transporter Type 1; D009004:Monosaccharide Transport Proteins / Q000235:genetics* / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism* / Q000821:virology; D018696:Neuroprotective Agents / Q000378:metabolism*; D009574:Nitro Compounds; D011422:Propionates / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley
D003292:Convulsants; D051272:Glucose Transporter Type 1; D009004:Monosaccharide Transport Proteins; D018696:Neuroprotective Agents; D009574:Nitro Compounds; D011422:Propionates; C495679:Slc2a1 protein, rat; C015392:3-nitropropionic acid