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. 2015 Oct;30(5):1269-74.
doi: 10.1007/s11011-015-9703-z. Epub 2015 Aug 13.

Myeloid Cell Leukemia 1 (Mcl(-1)) Protects Against 1-methyl-4-phenylpyridinium Ion (MPP+) Induced Apoptosis in Parkinson's Disease

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Myeloid Cell Leukemia 1 (Mcl(-1)) Protects Against 1-methyl-4-phenylpyridinium Ion (MPP+) Induced Apoptosis in Parkinson's Disease

Lijing Fan et al. Metab Brain Dis. .

Abstract

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.

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