Enhanced expression of glycine N-methyltransferase by adenovirus-mediated gene transfer in CNS culture is neuroprotective.
Glycine N-methyltransferase (GNMT) is the most abundant hepatic methyltransferase and plays important roles in regulating methyl group metabolism. In the central nervous system, GNMT expression is low and its function has not been revealed. The present study examines the effect of GNMT overexpression by adenovirus-mediated transfer in cortical mixed neuron-glial cultures. Infection of adenovirus encoding green fluorescence protein to cultures demonstrates high preference for non-neuronal cells. Optimal GNMT overexpression in cultures by adenoviral GNMT (Ad-GNMT) infection not only induces protein kinase C phosphorylation, but also increases neuronal/oligodendroglial survival. Furthermore, these Ad-GNMT-infected cultures are significantly resistant to H(2)O(2) toxicity and lipopolysaccharide stimulation. Conditioned media from Ad-GNMT-infected microglia also significantly enhance neuronal survival. Taken together, enhanced GNMT expression in mixed neuronal-glial cultures is neuroprotective, most likely mediated through non-neuronal cells.
Tsai
May-Jywan
MJ
Neural Regeneration Laboratory, Department of Neurosurgery, Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan.
Chen
Yi-Ming Arthur
YM
Weng
Ching-Feng
CF
Liou
Dann-Ying
DY
Yang
Hsin-Chun
HC
Chen
Chien-Hung
CH
Liao
Roanna I-Hsin
RI
Kuo
Fu-Shan
FS
Chiu
Chiuan-Wen
CW
Kuo
Huai-Sheng
HS
Huang
Ming-Chao
MC
Lin
Yi-Lo
YL
Lee
Meng-Jen
MJ
Kuo
Wen-Chun
WC
Huang
Wen-Cheng
WC
Cheng
Henrich
H
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D002470:Cell Survival; D002478:Cells, Cultured; D017077:Culture Media, Conditioned; D017931:DNA Primers; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D050938:Glycine N-Methyltransferase / Q000235:genetics*; D007150:Immunohistochemistry; D017628:Microglia / Q000166:cytology / Q000201:enzymology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction
D017077:Culture Media, Conditioned; D017931:DNA Primers; D050938:Glycine N-Methyltransferase