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Staphylococcus aureus Induces Goat Endometrial Epithelial Cells Apoptosis via the Autophagy and Endoplasmic Reticulum Stress Pathway.

ABSTRACT: Increasing evidence indicates that autophagy and endoplasmic reticulum (ER) stress are involved in the regulation of cell death; however, the role of autophagy and ER stress in Staphylococcus aureus-induced endometrial epithelial cell damage is still unelucidated. In the present study, our results showed that infection with S. aureus increased the cytotoxicity and the protein expression of Bax, caspase-3, and cleaved-PARP-1 in goat endometrial epithelial cells (gEECs). Moreover, after infection, the expression of LC3II and autophagosomes were markedly increased. The autophagosome inhibitor 3-methyladenine (3-MA) significantly decreased the cytotoxicity and the expression of caspase-3, and cleaved-PARP-1; however, the autophagosome-lysosome fusion inhibitor chloroquine (CQ) increased their expression. Additionally, the protein expression of GRP78, EIF2α, and ATF4 were also markedly increased after infection. The ER stress inhibitor 4-PBA decreased the cytotoxicity and the expression of LC3II and apoptosis-related proteins in S. aureus-infected gEECs. Collectively, our findings prove that the accumulation of autophagosomes exacerbated S. aureus-induced gEECs apoptosis, and that ER stress was involved in the regulation of the autophagy and apoptosis.

SUBMITTER: Yi Y

PROVIDER: S-EPMC8944437 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature

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Staphylococcus aureus Induces Goat Endometrial Epithelial Cells Apoptosis via the Autophagy and Endoplasmic Reticulum Stress Pathway.

Yi Yanyan Y Gao Kangkang K Zhang Ruixue R Lin Pengfei P Wang Aihua A Jin Yaping Y

Animals : an open access journal from MDPI 20220311 6

Increasing evidence indicates that autophagy and endoplasmic reticulum (ER) stress are involved in the regulation of cell death; however, the role of autophagy and ER stress in Staphylococcus aureus-induced endometrial epithelial cell damage is still unelucidated. In the present study, our results showed that infection with S. aureus increased the cytotoxicity and the protein expression of Bax, caspase-3, and cleaved-PARP-1 in goat endometrial epithelial cells (gEECs). Moreover, af ...[more]

PMID: 35327108

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Project description:Pancreatic ductal adenocarcinoma (PDAC) shows a high level of basal autophagy. Here we investigated the role of optineurin (OPTN) in PDAC cell lines, which is a prominent member of the autophagy system. To that purpose, mining of publically available databases showed that OPTN is highly expressed in PDAC and that high levels of expression are related to reduced survival. Therefore, the role of OPTN on proliferation, migration, and colony formation was investigated by transient knockdown in Miapaca, BXPC3, and Suit2-007 human PDAC cells. Furthermore, gene expression modulation in response to OPTN knockdown was assessed by microarray. The influence on cell cycle distribution and cell death signaling cascades was followed by FACS, assays for apoptosis, RT-PCR, and western blot. Finally, autophagy and ROS induction were screened by acridine orange and DCFH-DA fluorescent staining respectively. OPTN knockdown caused significant inhibition of colony formation, increased migration and no significant effect on proliferation in Miapaca, BXPC3 and Suit2-007 cells. The microarray showed modulation of 293 genes in Miapaca versus 302 in Suit2-007 cells, of which 52 genes overlapped. Activated common pathways included the ER stress response and chaperone-mediated autophagy, which was confirmed at mRNA and protein levels. Apoptosis was activated as shown by increased levels of cleaved PARP, Annexin V binding and nuclear fragmentation. OPTN knockdown caused no increased vacuole formation as assessed by acridine orange. Also, there was only marginally increased ROS production. Combination of OPTN knockdown with the autophagy inducer erufosine or LY294002, an inhibitor of autophagy, showed additive effects, which led us to hypothesize that they address different pathways. In conclusion, OPTN knockdown was related to activation of ER stress response and chaperone-mediated autophagy, which tend to confine the damage caused by OPTN knockdown and thus question its value for PDAC therapy.

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Staphylococcus aureus Induces Goat Endometrial Epithelial Cells Apoptosis via the Autophagy and Endoplasmic Reticulum Stress Pathway.

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<i>Staphylococcus aureus</i> Induces Goat Endometrial Epithelial Cells Apoptosis via the Autophagy and Endoplasmic Reticulum Stress Pathway.

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