Myeloid cell leukemia 1 (Mcl(-1)) protects against 1-methyl-4-phenylpyridinium ion (MPP+) induced apoptosis in Parkinson's disease.
The myeloid cell leukemia 1 (Mcl(-1)) is an anti-apoptotic member of the Bcl-2 family, which plays an essential role in protecting cells against apoptosis. The expression pattern and potential roles of Mcl(-1) in Parkinson's diseases (PD) are still unknown. In this study, our results indicated that 1-methyl-4-phenylpyridinium (MPP+) treatment augmented the expression of Mcl(-1) at both messenger RNA (mRNA) and protein levels in a dose-dependent manner in SH-SY5Y cells. Moreover, we observed increased phosphorylation of Elk-1at Ser383 as well as nuclear translocation of Elk-1 in exposure to MPP+ treatment. Importantly, the elevated expression of Mcl(-1) induced by MPP+ was abolished by knockdown of Elk-1. It was also found that inhibition of Mcl(-1) by small RNA transfection exacerbates MPP + -induced LDH release after 48 h incubation. In addition, Hoechst 33,258 nuclear staining results demonstrated that silence of Mcl(-1) induced a significant increase in apoptosis in cells when compared with the control condition. Mechanistically, the levels of cleaved Caspase3 and PARP were elevated in MPP+ treated cells, which was exacerbated by knockdown of Mcl(-1). These findings suggest that Mcl(-1) might be a potential therapeutic target for PD treatment.
Neurology Department, The 89th Hospital of People's Liberation Army, No. 256 Beigong west Street, Weifang City, Shandong, China.
Lijing
L
Fan
Li
L
Jiang
Zhongde
Z
Du
D015655:1-Methyl-4-phenylpyridinium / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D006801:Humans; D064549:Myeloid Cell Leukemia Sequence 1 Protein / Q000096:biosynthesis*; D010300:Parkinson Disease / Q000378:metabolism* / Q000517:prevention & control*
C579095:MCL1 protein, human; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D015655:1-Methyl-4-phenylpyridinium