Small interfering RNA targeting the PINK1 induces apoptosis in dopaminergic cells SH-SY5Y.
PTEN-induced kinase 1 (PINK1) is a recently identified gene, mutations of which cause levodopa-responsive parkinsonism. An over-expression of wild-type PINK1 protects neurons from stress-induced mitochondrial dysfunction and apoptosis. We studied the effects of PINK1 suppression using small interfering RNA (siRNA), which can inhibit PINK1 mRNA expression up to 87%, and decrease PINK1 protein up to 80% in human dopaminergic cell line SH-SY5Y. Incubation with PINK1 siRNA decreased SH-SY5Y cell viability and significantly increased MPP(+) or rotenone-induced cytotoxicity. Our results indicate that reduction in PINK1 expression can trigger apoptotic process that can be exacerbated by the presence of MPP(+) or rotenone. These findings support the hypothesis that PINK1 participates in the protection of dopaminergic neurons.
Deng
Hao
H
Department of Neurology, Baylor College of Medicine, USA.
Jankovic
Joseph
J
Guo
Yi
Y
Xie
Wenjie
W
Le
Weidong
W
D000595:Amino Acid Sequence; D017209:Apoptosis; D001483:Base Sequence; D045744:Cell Line, Tumor; D003001:Cloning, Molecular; D004298:Dopamine / Q000096:biosynthesis / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D008969:Molecular Sequence Data; D009474:Neurons / Q000378:metabolism* / Q000473:pathology*; D020648:Peptide Elongation Factor 1; D010445:Peptide Elongation Factors / Q000737:chemistry / Q000378:metabolism; D011494:Protein Kinases / Q000235:genetics* / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000737:chemistry / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D000099202:PTEN-Induced Putative Kinase
D004298:Dopamine; D020648:Peptide Elongation Factor 1; D010445:Peptide Elongation Factors; D011494:Protein Kinases; D034741:RNA, Small Interfering; D011994:Recombinant Proteins; D029701:Saccharomyces cerevisiae Proteins; D000099202:PTEN-Induced Putative Kinase; C080581:CAM1 protein, S cerevisiae