GAPDH knockdown rescues mesencephalic dopaminergic neurons from MPP+ -induced apoptosis.
Glyceraldehyde-3-phosphate dehydrogenase (GAPDH; EC 1.2.1.12) has a number of diverse functions apart from glycolytic function. We explored the possible involvement of GAPDH in 1-methyl-4-phenylpyridinium (MPP+)-induced death of mesencephalic dopaminergic neurons (MDNs) in culture. MPP+ (10 and 20 microM, 24 h) exposure selectively decreased the survival of tyrosine hydroxylase positive (TH+) MDNs, which manifested apoptotic features including shrinkage of the cell body, chromatin condensation and nuclear fragmentation. Two types of GAPDH antisense oligonucleotides almost completely rescued MDNs from MPP+ toxicity. GAPDH was strongly expressed in apoptotic TH+ neurons, and MPP+ exposure significantly increased the percentage of TH+ neurons in which GAPDH is over-expressed. Confocal microscopic analysis demonstrated the nuclear accumulation of GAPDH in neurons undergoing MPP+-induced apoptosis. These results suggest that MPP+ causes apoptosis of MDNs, concomitant with the over-expression and nuclear accumulation of GAPDH.
Fukuhara
Y
Y
Division of Neurology, Institute of Neurological Sciences, Tottori University Faculty of Medicine, 36-1 Nishimachi, Yonago 683-8504, Japan.
Takeshima
T
T
Kashiwaya
Y
Y
Shimoda
K
K
Ishitani
R
R
Nakashima
K
K
D015655:1-Methyl-4-phenylpyridinium / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D004298:Dopamine / Q000378:metabolism*; D005333:Fetus; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000037:antagonists & inhibitors* / Q000235:genetics; D006540:Herbicides / Q000494:pharmacology; D007150:Immunohistochemistry; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D010300:Parkinson Disease / Q000201:enzymology* / Q000503:physiopathology; D010302:Parkinson Disease, Secondary / Q000139:chemically induced; D051381:Rats; D017207:Rats, Sprague-Dawley; D013378:Substantia Nigra / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D006540:Herbicides; D008869:Microtubule-Associated Proteins; D016376:Oligonucleotides, Antisense; D014446:Tyrosine 3-Monooxygenase; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D015655:1-Methyl-4-phenylpyridinium; D004298:Dopamine