Curcumin can inhibit alpha-synuclein gene overexpression or mutation induced alpha-synuclein oligomers formation. - GreenMedInfo Summary
[Effect of curcumin on oligomer formation and mitochondrial ATP-sensitive potassium channels induced by overexpression or mutation of alpha-synuclein].
Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2015 Aug 10 ;32(4):462-7. PMID: 26252085
Tao Chen
OBJECTIVE: To investigate the effect of curcumin on oligomer formation and mitochondrial ATP-sensitive potassium channels (mitoKATP) induced by overexpression or mutation of alpha-synuclein.
METHODS: Recombinant plasmids alpha-synuclein-pEGFP-A53T and alpha-synuclein-pEGFP-WT were transfected into PC12 cells by lipofectamin method, and intervened by application of curcumin (20μmol/L) and 5-hydroxydecanoate (5-HD). Oligomer formation in the cultured cells was identified by Western blotting and Dot blotting. Cytotoxicity and apoptosis of the PC12 cells were measured by lactate dehydrogenase (LDH) and JC-1 assays. mitoKATP were identified by Western blotting and whole cellpatch clamp.
RESULTS: Curcumin has significantly reduced the oligomer formation induced by overexpression or mutation of alpha-synuclein in the cultured cells. LDH has decreased by 36.3% and 23.5%, and red/green fluorescence ratio of JC-1 was increased respectively by 48.46% and 50.33% after application of curcumin (P<0.05). Protein expression of Kir6.2 has decreased and mitoKATP channel current has significantly increased (P<0.05).
CONCLUSION: Curcumin can inhibit alpha-synuclein gene overexpression or mutation induced alpha-synuclein oligomers formation. It may block apoptosis induced by wild-type overexpression or mutation of alpha-synuclein. By stabilizing mitochondrial membrane potential. Opening of mitoKATP channel may have been the initiating protective mechanism of apoptosis induced by wild-type overexpression or mutation of alpha-synuclein. Curcumin may antagonize above cytotoxicity through further opening the mitoKATP channel.
