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
N1 - Funding Information:
We thank Professor Kunio Yagi for his helpful discussion to prepare this manuscript. This work was supported by a Grant-in-Aid for Scientific Research (Y.A., No. 09670859) and for Priority Area from the Ministry of Education, Science and Education, Japan (M.N.), and the Grant for Longevity Sciences from the Ministry of Health and Welfare, Japan (9C-03 for M.N. and 9C-02 for W.M.).
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
SN - 0304-3940
VL - 267
SP - 153
EP - 156
JO - Neuroscience Letters
JF - Neuroscience Letters
IS - 3
ER -