ERK1/2 and the Bcl-2 Family Proteins Mcl-1, tBid, and Bim Are Involved in Inhibition of Apoptosis During Persistent Chlamydia psittaci Infection

Li, Li; Wang, Chuan; Wen, Yang; Hu, Yuming; Xie, Yanping; Xu, Man; Liang, Mingxing; Liu, Wei; Liu, Liangzhuan; Wu, Yimou

doi:10.1007/s10753-018-0785-8

Cited by 8 publications

(7 citation statements)

References 46 publications

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“…Furthermore, p27 is a CDK inhibitor that has a negative regulatory effect on proliferation and is a downstream target of FOXO1; consequently, FOXO1 inhibits cell proliferation by upregulating p27 (39)(40)(41)(42). The Bim protein belongs to the Bcl-2 protein family and exerts a pro-apoptotic effect on cells (43,44); previous studies have confirmed that FOXO1 regulates cell apoptosis through its downstream targets, including Bim (45,46). The present study confirmed that propofol may regulate miR-374a/FOXO1 signaling to promote the expression of p27 and Bim, and to inhibit the proliferation and promote the apoptosis of ovarian cancer cells, thereby enhancing the sensitivity of ovarian cancer cells to ddP.…”

Section: Discussionmentioning

confidence: 99%

Propofol inhibits proliferation and cisplatin resistance in ovarian cancer cells through regulating the microRNA‑374a/forkhead box O1 signaling axis

Sun

Peng

et al. 2020

Mol Med Report

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ovarian cancer is a prominent disease that demonstrates high incidence rates in women and often presents multidrug resistance. Propofol has been demonstrated to suppress the malignancy of various types of human cancer; however, the underlying molecular mechanisms of propofol in ovarian cancer remain largely unknown. The present study aimed to investigate whether and how propofol inhibits proliferation and cisplatin (ddP) resistance in ovarian cancer cells. ovarian cancer cell viability was assessed by the cell counting kit-8 assay; apoptosis and cell cycle progression were determined by flow cytometry; the relative expression levels of microRNA (miR)-374a and forkhead box O1 (FOXO1) were analyzed using reverse transcription-quantitative Pcr; the binding ability of miR-374a to FOXO1 was assessed by the dual-luciferase reporter assay; cellular sensitivity to ddP was detected using the MTT assay; and finally, the protein expression levels of FOXO1, p27, and Bcl-2-like-protein 11 (Bim) were analyzed by western blotting. Propofol reduced viability, promoted apoptosis and decreased mir-374a expression levels in A2780 cells. In addition, the viability of a2780/ddP cells in the propofol + ddP treatment group was significantly inhibited, and the apoptotic rate was increased. In addition, miR-374a overexpression increased cell viability and the proportion of cells in the S phase, and decreased the proportion of cells in the G0/G1 phase. conversely, genetic knockdown of miR-374a exerted the opposite effects on cell viability and cell cycle progression. Moreover, mir-374a was demonstrated to bind to FOXO1. Propofol promoted the expression of FOXO1, p27 and Bim, induced cell cycle arrest and decreased ovarian cancer cell viability. in addition, treatment with propofol and DDP regulated FOXO1 and increased apoptosis of ovarian cancer cells. in conclusion, propofol downregulated mir-374a and modulated the FOXO1 pathway to reduce proliferation and DDP resistance in ovarian cancer cells.

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Section: Discussionmentioning

confidence: 99%

Propofol inhibits proliferation and cisplatin resistance in ovarian cancer cells through regulating the microRNA‑374a/forkhead box O1 signaling axis

Sun

Peng

et al. 2020

Mol Med Report

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“…Inhibition of host cell apoptosis is a persistent C. trachomatis infection mechanisms [ 42 ]. Current studies have confirmed that persistent C. trachomatis infection affects some apoptotic signaling pathways [ 43–45 ].…”

Section: Discussionmentioning

confidence: 99%

LncRNA ZEB1-AS1/miR-1224-5p / MAP4K4 axis regulates mitochondria-mediated HeLa cell apoptosis in persistent Chlamydia trachomatis infection

et al. 2022

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Persistent infection of Chlamydia trachomatis is thought to be responsible for the debilitating sequelae of blinding trachoma and infertility. Inhibition of host cell apoptosis is a persistent C. trachomatis infection mechanism. ZEB1-AS1 is a long non-coding RNA (lncRNA), which was up-regulated in persistent C. trachomatis infection in our previous work. In this study, we investigated the role of ZEB1-AS1 in persistent infection and the potential mechanisms. The results showed that ZEB1-AS1 was involved in the regulation of apoptosis, and targeted silencing of ZEB1-AS1 could increase the apoptosis rate of persistently infected cells. Mechanically, interference ZEB1-AS1 caused an apparent down-regulation of the Bcl-2/Bax ratio and the repression of the mitochondrial membrane potential with the remarkable release of cytochrome c, resulting in the significant elevation level of caspase-3 activation. Meanwhile, the luciferase reporter assay confirmed that ZEB1-AS1 acted as a sponge for miR-1224-5p to target MAP4K4. The regulatory effect of miR-1224-5p/MAP4K4 on persistent infection-induced antiapoptosis was regulated by ZEB1-AS1. In addition, ZEB1-AS1 inhibited the apoptosis of Chlamydia -infected cells by activating the MAPK/ERK pathway. In conclusion, we found a new molecular mechanism that the ZEB1-AS1/miR-1224-5p/MAP4K4 axis contributes to apoptosis resistance in persistent C. trachomatis infection. This work may help understand the pathogenic mechanisms of persistent C. trachomatis infection and reveal a potential therapeutic strategy for its treatment.

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“…Previous studies have shown that some Inc proteins can inhibit host cell apoptosis, which is essential for Chlamydia infection (Li et al, 2018). C. trachomatis IncG interacts with the mammalian 14-3-3b protein in HeLa cells, and 14-3-3b in turn recruits Bad (a pro-apoptotic protein) to the chlamydial inclusion complex, resulting in inhibition of host cell apoptosis (Scidmore and Hackstadt, 2001).…”

Section: Discussionmentioning

confidence: 99%

“…A decrease in MMP is a characteristic of the early stages of mitochondrial-dependent apoptosis, in which the up-regulation of the Bax/Bcl-2 ratio causes Cyt.c release into the cytoplasm, and then Caspase-9 and Caspase-3 are activated, accompanied by the lysis of PARP, which eventually leads to cell apoptosis (Bi et al, 2018;Ye et al, 2019). Chlamydia can maintain MMP stability, which might be inseparable from the mechanisms of persistent infection and resistance to host cell apoptosis (Li et al, 2018). CPSIT_0846 can prevent CCCP-induced mitochondrial membrane potential reduction and inhibit the release of Cyt.c into the cytoplasm, which indicates that CPSIT_0846 may inhibit host cell apoptosis by acting on mitochondrial-mediated signaling pathways.…”

Section: Discussionmentioning

confidence: 99%

“…C. trachomatis can activate PDPK1-MYC, enhance the binding of hexase II (HKII) to mitochondria, and thereby resist apoptosis (Al-Zeer et al, 2017). C. psittaci can inhibit HeLa cell apoptosis through the mitochondria-mediated apoptosis pathway, and this process is regulated by ERK1/2 and Bcl-2 family proteins (Li et al, 2018). Chlamydial Inc proteins also participate in the regulation of host cell apoptosis.…”

Section: Introductionmentioning

confidence: 99%

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

Tang

Chen

et al. 2021

Front. Cell. Infect. Microbiol.

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Chlamydia psittaci is an important zoonotic factor associated with human and animal atypical pneumonia. Resisting host cell apoptosis is central to sustaining Chlamydia infection in vivo. Chlamydia can secrete inclusion membrane proteins (Incs) that play important roles in their development cycle and pathogenesis. CPSIT_0846 is an Inc protein in C. psittaci 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.

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ERK1/2 and the Bcl-2 Family Proteins Mcl-1, tBid, and Bim Are Involved in Inhibition of Apoptosis During Persistent Chlamydia psittaci Infection

Cited by 8 publications

References 46 publications

Propofol inhibits proliferation and cisplatin resistance in ovarian cancer cells through regulating the microRNA‑374a/forkhead box O1 signaling axis

Propofol inhibits proliferation and cisplatin resistance in ovarian cancer cells through regulating the microRNA‑374a/forkhead box O1 signaling axis

LncRNA ZEB1-AS1/miR-1224-5p / MAP4K4 axis regulates mitochondria-mediated HeLa cell apoptosis in persistent Chlamydia trachomatis infection

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

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