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Antiapoptotic property of human α‐synuclein in neuronal cell lines is associated with the inhibition of caspase‐3 but not caspase‐9 activity
Author(s) -
Li Wenxue,
Lee Michael K.
Publication year - 2005
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.1471-4159.2005.03146.x
Subject(s) - apoptosis , synucleinopathies , caspase , microbiology and biotechnology , caspase 3 , cell culture , programmed cell death , biology , mutant , caspase 9 , caspase 2 , intrinsic apoptosis , alpha synuclein , biochemistry , parkinson's disease , medicine , genetics , disease , gene
Abnormalities of α‐synuclein (α‐Syn) are mechanistically linked to Parkinson's disease (PD) and other α‐synucleinopathies. To gain additional insights into the relationships between α‐Syn expression and cell death, we examined the effects of expressing human α‐Syn (Huα‐Syn) variants on the cellular vulnerability to apoptotic stimuli. We show that the expression of wild‐type (WT) and A30P mutant, but not A53T mutant, Huα‐Syn leads to the protection of neuronal cell lines from apoptosis but not necrosis. Significantly, Huα‐Syn did not protect non‐neuronal cell lines from apoptosis. We also show that A53T mutant is a loss of function in regards to the antiapoptotic property since the expression of WT Huα‐Syn with an excess of A53T mutant Huα‐Syn leads to protection of the cells from apoptosis. The antiapoptotic property is specific to human α‐Syn as neither β‐Syn nor mouse α‐Syn protected cells from apoptosis, and the carboxy‐terminal 20 amino acids are required for the antiapoptotic property. Analyses of capase‐3 and caspase‐9 activation reveal that the antiapoptotic property of Huα‐Syn in neuronal cell lines is associated with the attenuation of caspase‐3 activity without affecting the caspase‐9 activity or the levels of cleaved, active caspase‐3. We conclude that Huα‐Syn modulates the activity of cleaved caspase‐3 product in neuronal cell lines.