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Titolo:
Transfection-enforced Bcl-2 overexpression and an anti-Parkinson drug, rasagiline, prevent nuclear accumulation of glyceraldehyde-3-phosphate dehydrogenase induced by an endogenous dopaminergic neurotoxin, N-methyl(R)salsolinol
Autore:
Maruyama, W; Akao, Y; Youdim, MBH; Davis, BA; Naoi, M;
Indirizzi:
Natl Inst Longev, Dept Basic Gerontol, Biochem & Metab Lab, Aichi, Japan Natl Inst Longev Aichi Japan erontol, Biochem & Metab Lab, Aichi, Japan Gifu Int Inst Biotechnol, Gifu, Japan Gifu Int Inst Biotechnol Gifu Japan fu Int Inst Biotechnol, Gifu, Japan Technion Israel Inst Technol, Fac Med, Eve Topf & NPF Ctr, Haifa, Israel Technion Israel Inst Technol Haifa Israel Topf & NPF Ctr, Haifa, Israel Univ Saskatchewan, Dept Psychiat, Saskatoon, SK S7N 0W0, Canada Univ Saskatchewan Saskatoon SK Canada S7N 0W0 skatoon, SK S7N 0W0, Canada Inst Appl Biochem, Dept Brain Sci, Gifu 5050116, Japan Inst Appl Biochem Gifu Japan 5050116 Dept Brain Sci, Gifu 5050116, Japan
Titolo Testata:
JOURNAL OF NEUROCHEMISTRY
fascicolo: 4, volume: 78, anno: 2001,
pagine: 727 - 735
SICI:
0022-3042(200108)78:4<727:TBOAAA>2.0.ZU;2-I
Fonte:
ISI
Lingua:
ENG
Soggetto:
ALIPHATIC N-METHYLPROPARGYLAMINES; NEUROBLASTOMA SH-SY5Y CELLS; CYTOSINE-ARABINOSIDE; NEURONAL APOPTOSIS; GLYCOLYTIC-ENZYMES; FAMILY PROTEINS; B INHIBITORS; DISEASE; GAPDH; DEATH;
Keywords:
apoptosis; Bcl-2; glyceraldehyde-3-phosphate dehydrogenase; N-methyl(R)salsolinol; Parkinson's disease; rasagiline;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
58
Recensione:
Indirizzi per estratti:
Indirizzo: Naoi, M Inst Appl Biochem, Dept Brain Sci, Yagi Mem Pk, Gifu 5050116, Japan Inst Appl Biochem Yagi Mem Pk Gifu Japan 5050116 u 5050116, Japan
Citazione:
W. Maruyama et al., "Transfection-enforced Bcl-2 overexpression and an anti-Parkinson drug, rasagiline, prevent nuclear accumulation of glyceraldehyde-3-phosphate dehydrogenase induced by an endogenous dopaminergic neurotoxin, N-methyl(R)salsolinol", J NEUROCHEM, 78(4), 2001, pp. 727-735

Abstract

An endogenous dopaminergic neurotoxin, N-methyl(R)salsolinol, was found toinduce apoptosis in human dopaminergic SH-SY5Y cells by step-wise activation of apoptotic cascade; collapse in mitochondrial membrane potential, Delta Psim, activation of caspases, and fragmentation of DNA. Recently, accumulation of gylceraldehyde-3-phosphate dehydrogenase (GAPDH) in nuclei was proposed to play an important role in apoptosis. In this paper, involvement ofGAPDH in apoptosis induced by N-methyl(R)salsolinol was studied. The isoquinoline reduced Delta Psim within 3 h, as detected by a fluorescence indicator, JC-1, then after 16 h incubation, GAPDH accumulated in nuclei by detection with immunostaining. To clarify the role of GAPDH in apoptotic process, a stable cell line of Bcl-2 overexpressed SH-SY5Y cells was established. Overexpression of Bcl-2 prevented the decline in Delta Psim and also apoptotic DNA damage induced by N-methyl(R)salsolinol. In Bcl-2 transfected cells, nuclear translocation of GAPDH was also completely suppressed. In addition, a novel antiparkinsonian drug, rasagiline, prevented nuclear accumulation of GAPDH induced by N-methyl(R)salsolinol in control cells. These resultssuggest that GAPDH may accumulate in nuclei as a consequence of signal transduction, which is antagonized by anti-apoptotic Bcl-2 protein family and rasagiline. The results are discussed in concern to intracellular mechanismunderlying anti-apoptotic function of rasagiline analogues.

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Documento generato il 02/07/20 alle ore 22:09:45