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 overexpressio...

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Published in:Annals of the New York Academy of Sciences 2010-06, Vol.1199 (1), p.194-203
Main Authors: Tsai, May-Jywan, Chen, Yi-Ming Arthur, Weng, Ching-Feng, Liou, Dann-Ying, Yang, Hsin-Chun, Chen, Chien-Hung, Liao, Roanna I-Hsin, Kuo, Fu-Shan, Chiu, Chiuan-Wen, Kuo, Huai-Sheng, Huang, Ming-Chao, Lin, Yi-Lo, Lee, Meng-Jen, Kuo, Wen-Chun, Huang, Wen-Cheng, Cheng, Henrich
Format: Article
Language:English
Subjects:
Adenoviridae - genetics
adenovirus
Adenoviruses
Animals
Base Sequence
Blotting, Western
Cell Survival
Cells, Cultured
Central nervous system
Culture
Culture Media, Conditioned
DNA Primers
Gene Transfer Techniques
Genetic Vectors
Glycine
Glycine N-Methyltransferase - genetics
GNMT
Immunohistochemistry
Kinases
lipopolysaccharide
Microglia - cytology
Microglia - enzymology
neuron-glia interaction
Proteins
Rats
Rats, Sprague-Dawley
Reverse Transcriptase Polymerase Chain Reaction
Stimulation
Survival
Toxicity
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Summary: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 H2O2 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.
ISSN:0077-8923
1749-6632
DOI:10.1111/j.1749-6632.2009.05169.x