Apoptosis induced by an endogenous neurotoxin, N-methyl(R)salsolinol, is mediated by activation of caspase 3.
An endogenous neurotoxin, N-methyl(R)salsolinol, has been proved to be involved in the pathogenesis of Parkinson's disease. Increased level of N-methyl(R)salsolinol in the cerebrospinal fluid and high activity of its synthesizing (R)salsolinol N-methyltransferase in lymphocytes were confirmed in the majority of parkinsonian patients. Recently this neurotoxin was found to induce apoptosis in human dopaminergic neuroblastoma SH-SY5Y cells. In this study, we tried to elucidate the intracellular mechanism of apoptosis induced by N-methyl(R)salsolinol, and proved activation of caspase 3 after incubation with this toxin by Western blot analysis. Further, a caspase 3 inhibitor, acetyl-L-aspartyl-L-glutamyl-L-valyl-L-aspartic aldehyde, prevented the nucleosomal DNA fragmentation completely. These results demonstrate that caspase 3 mediates apoptosis induced by an endogenous neurotoxin, N-methyl(R)salsolinol, which may cause apoptotic cell death of dopamine neurons in Parkinson's disease.
Akao
Y
Y
Gifu International Institute of Biotechnology, Mitake, Japan.
Nakagawa
Y
Y
Maruyama
W
W
Takahashi
T
T
Naoi
M
M
D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D053148:Caspase 3; D061945:Caspase Inhibitors; D020169:Caspases / Q000502:physiology*; D053938:DNA Fragmentation / Q000187:drug effects; D004789:Enzyme Activation; D004792:Enzyme Precursors / Q000187:drug effects / Q000502:physiology; D006801:Humans; D009498:Neurotoxins / Q000494:pharmacology*; D009842:Oligopeptides / Q000494:pharmacology; D010300:Parkinson Disease / Q000201:enzymology / Q000209:etiology; D012490:Salsoline Alkaloids / Q000494:pharmacology*; D044005:Tetrahydroisoquinolines; D014407:Tumor Cells, Cultured
D061945:Caspase Inhibitors; D004792:Enzyme Precursors; D009498:Neurotoxins; D009842:Oligopeptides; D012490:Salsoline Alkaloids; D044005:Tetrahydroisoquinolines; C099158:acetyl-aspartyl-glutamyl-valyl-aspartal; C032837:salsoline; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases