The Hypothetical Inclusion Membrane Protein CPSIT_0846 Regulates Mitochondrial-Mediated Host Cell Apoptosis the ERK/JNK Signaling Pathway.

is an important zoonotic factor associated with human and animal atypical pneumonia. Resisting host cell apoptosis is central to sustaining infection . can secrete inclusion membrane proteins (Incs) that play important roles in their development cycle and pathogenesis. CPSIT_0846 is an Inc protein in identified by our team in previous work. In the current study, we investigated the regulatory role of CPSIT_0846 in HeLa cell apoptosis, and explored potential mechanisms. The results showed that HeLa cells treated with CPSIT_0846 contained fewer apoptotic bodies and exhibited a lower apoptotic rate than untreated cells either with Hoechst 33258 fluorescence staining or flow cytometry with or without induction by staurosporine (STS). CPSIT_0846 could increase the phosphorylation of the extracellular signal-regulated kinases 1/2 (ERK1/2) or stress-activated protein kinases/c-Jun amino-terminal kinases (SAPK/JNK) signaling pathways, and the Bcl-2 associated X protein (Bax)/B cell lymphoma 2 (Bcl-2) ratio, levels of cleaved caspase-3/9 and cleaved Poly-ADP-ribose polymerase (PARP) were significantly up-regulated following inhibition of ERK1/2 or SAPK/JNK pathways with U0126 or SP600125. After carbonyl cyanide 3-chlorophenylhydrazone (CCCP) treatment, the mitochondrial membrane potential (MMP) of cells was significantly decreased in control group, but stable in the CPSIT_0846 treated one, and less cytochrome c (Cyt.c) was released into the cytoplasm. Inhibition of the ERK1/2 or SAPK/JNK pathway significantly decreased the JC-1 red-green fluorescence signal, and promoted Cyt.c discharge into the cytoplasm in HeLa cells treated with CPSIT_0846. In conclusion, CPSIT_0846 can regulate mitochondrial pathway-mediated apoptosis in HeLa cells by activating the ERK/JNK signaling pathway.