TY - JOUR
T1 - Apoptosis induced by an endogenous neurotoxin, N-methyl(R)salsolinol, is mediated by activation of caspase 3
AU - Akao, Yukihiko
AU - Nakagawa, Yoshihito
AU - Maruyama, Wakako
AU - Takahashi, Tsutomu
AU - Naoi, Makoto
PY - 1999/6/4
Y1 - 1999/6/4
N2 - 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.
AB - 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.
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U2 - 10.1016/S0304-3940(99)00361-4
DO - 10.1016/S0304-3940(99)00361-4
M3 - Article
C2 - 10380999
AN - SCOPUS:0033522852
VL - 267
SP - 153
EP - 156
JO - Neuroscience Letters
JF - Neuroscience Letters
SN - 0304-3940
IS - 3
ER -