Myeloid cell leukemia 1 (Mcl−1) protects against 1-methyl-4-phenylpyridinium ion (MPP+) induced apoptosis in Parkinson’s disease

• DOI: 10.1007/s11011-015-9703-z
• Publication Date: 2015-08-12T01:48:30Z
• Authors: Lijing Fan; Li Jiang; Zhongde Du
• Keywords: 0301 basic medicine; 1-Methyl-4-phenylpyridinium; 03 medical and health sciences; Dose-Response Relationship, Drug; Cell Line, Tumor; Humans; Myeloid Cell Leukemia Sequence 1 Protein; Apoptosis; Parkinson Disease; 3. Good health

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.