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Type A monoamine oxidase is the target of an endogenous dopaminergic neurotoxin, N ‐methyl( R )salsolinol, leading to apoptosis in SH‐SY5Y cells
Author(s) -
Yi Hong,
Akao Yukihiro,
Maruyama Wakako,
Chen Kavin,
Shih Jean,
Naoi Makoto
Publication year - 2006
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2005.03573.x
Subject(s) - neurotoxin , dopaminergic , monoamine oxidase b , monoamine oxidase , apoptosis , monoamine oxidase a , biology , endogeny , selegiline , mitochondrion , sh sy5y , programmed cell death , monoamine neurotransmitter , dopamine , mptp , microbiology and biotechnology , biochemistry , endocrinology , medicine , cell culture , parkinson's disease , enzyme , neuroblastoma , receptor , serotonin , genetics , disease
Mitochondrial monoamine oxidase (MAO) has been considered to be involved in neuronal degeneration either by increased oxidative stress or protection with the inhibitors of type B MAO (MAO‐B). In this paper, the role of type A MAO (MAO‐A) in apoptosis was studied using human neuroblastoma SH‐SY5Y cells, where only MAO‐A is expressed. An endogenous dopaminergic neurotoxin, N ‐methyl( R )salsolinol, an MAO‐A inhibitor, reduced membrane potential, ΔΨm, in isolated mitochondria, and induced apoptosis in the cells, which 5‐hydroxytryptamine, an MAO‐A substrate, prevented. In contrast, β‐phenylethylamine, an MAO‐B substrate, did not suppress the ΔΨm decline by N ‐methyl( R )salsolinol. The binding of N ‐methyl( R )salsolinol to mitochondria was inhibited by clorgyline, a MOA‐A inhibitor, but not by (–)deprenyl, an MAO‐B inhibitor. RNA interference targeting MAO‐A significantly reduced the binding of N ‐methyl( R )salsolinol with simultaneous reduction in the MAO activity. To examine the intervention of MAO‐B in the apoptotic process, human MAO‐B was transfected to SH‐SY5Y cells, but the sensitivity to N ‐methyl( R )salsolinol was not affected, even although the activity and protein of MAO increased markedly. These results demonstrate a novel function of MAO‐A in the binding of neurotoxins and the induction of apoptosis, which may account for neuronal cell death in neurodegenerative disorders, including Parkinson's disease.