TLR2/NF⁃κB通路介导MPP+ 诱导的RSC96细胞凋亡与自噬.

Objective：To investigate the relationship between TLR2/NF ⁃ κB signaling pathway and the apoptosis and autophagy dysfunction of RSC96 cells induced by 1⁃methyl⁃4⁃phenyl⁃pyridinium(MPP+). Methods：RSC96 cells were divided into the PBS group， MPP+ group，and MPP+ + CU ⁃ CPT22 group. Cell survival rate was detected using CCK ⁃ 8 after treatment with different MPP+ concentrations(0.1，0.3，0.5，0.7，0.9 mmol/L）. Cell apoptosis was detected by TUNEL staining. RT⁃qPCR was performed to detect the TLR2 mRNA level. Western blot was performed to detect the expression levels of apoptosis related indicators Bcl ⁃ 2/Bax，cleaved caspase⁃3/caspase⁃3，autophagy⁃related indicators LC3II/LC3I and P62，as well as TLR2 and p⁃NF⁃κB/NF⁃κB. Results：Compared with the PBS group，the cell viability of the MPP+ group decreased in a concentration ⁃ dependent manner，the number of TUNEL ⁃ staining positive cells increased，the ratio of Bcl⁃2/Bax decreased while cleaved caspase⁃3/caspase⁃3 ratio increased，as well as had a decrease in the ratio of LC3Ⅱ/LC3Ⅰ and an increase in P62 and p ⁃NF ⁃κB/NF ⁃κB ratio elvel. RT ⁃qPCR and Western blot results showed that MPP+ upregulated the expression of TLR2. In addition，compared with the MPP+ group，the MPP+ + CU ⁃ CPT22 group showed a decrease in the number of TUNEL⁃staining positive cells，an increase in Bcl⁃2/Bax level，and a decrease in cleaved caspase⁃3/ caspase ⁃ 3 ratio. Meanwhile，LC3 Ⅱ/LC3 Ⅰ ratio was increased，and the P62 expression level was decreased. Conclusion：MPP+ stimulation induced apoptosis and the imbalance of autophagy in RSC96 cells，and the mechanism may be related to the activation of the TLR2/NF⁃κB signaling pathway. [ABSTRACT FROM AUTHOR]