title: Enhanced expression of glycine N-methyltransferase by adenovirus-mediated gene transfer in CNS culture is neuroprotective.
abstract: 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.
authors.affiliation: Neural Regeneration Laboratory, Department of Neurosurgery, Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: May-Jywan
authors.initials: MJ
authors.lastname: Tsai
authors.forename: Yi-Ming Arthur
authors.initials: YM
authors.lastname: Chen
authors.forename: Ching-Feng
authors.initials: CF
authors.lastname: Weng
authors.forename: Dann-Ying
authors.initials: DY
authors.lastname: Liou
authors.forename: Hsin-Chun
authors.initials: HC
authors.lastname: Yang
authors.forename: Chien-Hung
authors.initials: CH
authors.lastname: Chen
authors.forename: Roanna I-Hsin
authors.initials: RI
authors.lastname: Liao
authors.forename: Fu-Shan
authors.initials: FS
authors.lastname: Kuo
authors.forename: Chiuan-Wen
authors.initials: CW
authors.lastname: Chiu
authors.forename: Huai-Sheng
authors.initials: HS
authors.lastname: Kuo
authors.forename: Ming-Chao
authors.initials: MC
authors.lastname: Huang
authors.forename: Yi-Lo
authors.initials: YL
authors.lastname: Lin
authors.forename: Meng-Jen
authors.initials: MJ
authors.lastname: Lee
authors.forename: Wen-Chun
authors.initials: WC
authors.lastname: Kuo
authors.forename: Wen-Cheng
authors.initials: WC
authors.lastname: Huang
authors.forename: Henrich
authors.initials: H
authors.lastname: Cheng
mesh_terms: 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
chemical_list: D017077:Culture Media, Conditioned; D017931:DNA Primers; D050938:Glycine N-Methyltransferase