Quinocetone triggered ER stress-induced autophagy via ATF6/DAPK1-modulated mAtg9a trafficking

Zhou, Yan; Zhang, Shen; Dai, Chongshan; Tang, Shusheng; Yang, Xiayun; Li, Daowen; Zhao, Kai; Xiao, Xilong

doi:10.1007/s10565-016-9323-3

Cited by 25 publications

(20 citation statements)

References 40 publications

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“…Furthermore, the hepatitis C virus core protein was found to activate autophagy through ATF6 pathway (54). Also, autophagy triggered by quinocetone via the ATF6 upregulated the expression of deathassociated protein kninase 1 (55). In this work, we verified in vivo and in vitro that ORMDL3 modulates ERs mainly through ATF6 pathway, but not PERK and IRE1-XBP1 pathways.…”

Section: Discussionsupporting

confidence: 52%

ORMDL3 Facilitates the Survival of Splenic B Cells via an ATF6α–Endoplasmic Reticulum Stress–Beclin1 Autophagy Regulatory Pathway

Deng

Bian

et al. 2017

The Journal of Immunology

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The genetic association of orosomucoid-like 3 (ORMDL3) with an array of immunoinflammatory disorders has been recently unraveled in multiple ethnic groups, and functional exploration has received attention of the particular relevance of this gene in endoplasmic reticulum stress, lipid metabolism, and inflammatory response. In this study, we demonstrated the upregulation of ORMDL3 in both patients with systemic lupus erythematosus and lupus mice compared with controls. By establishing ORMDL3 knockout mice (), we showed that silencing Ormdl3 in vivo significantly decreased the proportions of mature B lymphocytes and transitional 2B cells in spleen and B1a cells from abdominal cavity perfusion fluid, the secretion of IgG and IgM, and the expression of Baff. Additionally, knockdown of Ormdl3 augmented the apoptosis of total splenic cells and splenic CD19 B cells but did not affect B cell proliferation and cell cycle. Subsequently, we in vitro and in vivo demonstrated that ORMDL3 potentially mediates the autophagy via the ATF 6-Beclin1 autophagy pathway, and it facilitates the survival of splenic B cells via promoting autophagy and suppressing apoptosis. Taken together, we uncovered a role of ORMDL3 in fine-tuning B cell development and survival, besides highlighting a potential mechanism by which ORMDL3 regulates autophagy via ATF6 pathway.

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Section: Discussionsupporting

confidence: 52%

ORMDL3 Facilitates the Survival of Splenic B Cells via an ATF6α–Endoplasmic Reticulum Stress–Beclin1 Autophagy Regulatory Pathway

Deng

Bian

et al. 2017

The Journal of Immunology

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“…In these cells, resveratrol treatment increased levels of LC3-II and GFP-LC3 punctate foci, reflecting its subcellular localization in autophagosomes, whereas DAPK1 silencing significantly attenuated observed effects. In agreement with that study, knockdown of DAPK1 in the hepatoma cell line HepG2 significantly decreased the LC3-II/I ratio in quinocetone-induced autophagy (Zhou et al 2016). Together, these studies and our results in first-trimester placentas suggest that DAPK1 expression is directly associated with LC3-II levels in the autophagy process.…”

Section: Discussionsupporting

confidence: 87%

Placental DAPK1 and autophagy marker LC3B-II are dysregulated by TNF-α in a gestational age-dependent manner

Prokesch

Blaschitz

Bauer

et al. 2017

Histochem Cell Biol

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Autophagy, a cell-survival process responsible for degradation of protein aggregates and damaged organelles, is increasingly recognized as another mechanism essential for human placentation. A substantial body of experiments suggests inflammation and oxidative stress as the underlying stimuli for altered placental autophagy, giving rise to placenta dysfunction and pregnancy pathologies. Here, the hypothesis is tested whether or not pro-inflammatory cytokines interleukin (IL)-6 and tumor necrosis factor (TNF)-α are able to influence the expression profile of autophagy genes in human first-trimester villous placenta. Autophagy-focused qPCR arrays identified substantial downregulation of death-associated protein kinase 1 (DAPK1) in first-trimester placental explants in response to IL-6 and TNF-α, respectively. Immunohistochemistry of placental explants detected considerable DAPK1 staining in placental macrophages, villous cytotrophoblasts and less intense in the syncytiotrophoblast. Both immunohistochemistry and Western blot showed decreased DAPK1 protein in TNF-α-treated placental explants compared to control. On cellular level, DAPK1 expression decreased in SGHPL-4 trophoblasts in response to TNF-α. Observed changes in the expression profile of autophagy-related genes were reflected by significantly decreased lipidation of autophagy marker microtubule-associated protein light chain 3 beta (LC3B-II) in first trimester placental explants in response to TNF-α. Analysis of TNF-α-treated term placental explants showed decreased DAPK1 protein, whereas in contrast to first-trimester LC3B expression and lipidation increased. Immunohistochemistry of placental tissues from early-onset preeclampsia (PE) showed less DAPK1 staining, when compared to controls. Accordingly, DAPK1 mRNA and protein were decreased in primary trophoblasts isolated from early-onset PE, while LC3B-I and -II were increased. Results from this study suggest that DAPK1, a regulator of apoptosis, autophagy and programmed necrosis, decreases in human placenta in response to elevated maternal TNF-α, irrespective of gestational age. In contrast, TNF-α differentially regulates levels of autophagy marker LC3B in human placenta over gestation.

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“…The endoplasmic reticulum is a large membrane-enclosed cellular organelle in eukaryotes to precede folding of membrane and secrete proteins. Physiologic and pathological stresses such as aggregate-prone proteins, glucose deprivation, hypoxia, and efflux from the ER can lead to the failure of protein folding and then causing ER stress 37 , 39 . With the accumulation of unfolded proteins and damaged organelles during ER stress, autophagy can be activated by the unfolded protein response (UPR) 40 .…”

Section: Discussionmentioning

confidence: 99%

Zearalenone altered the cytoskeletal structure via ER stress- autophagy- oxidative stress pathway in mouse TM4 Sertoli cells

Zheng

Wang

et al. 2018

Sci Rep

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The aim of this study was to investigate the molecular mechanisms of the destruction of cytoskeletal structure by Zearalenone (ZEA) in mouse-derived TM4 cells. In order to investigate the role of autophagy, oxidative stress and endoplasmic reticulum(ER) stress in the process of destruction of cytoskeletal structure, the effects of ZEA on the cell viability, cytoskeletal structure, autophagy, oxidative stress, ER stress, MAPK and PI3K- AKT- mTOR signaling pathways were studied. The data demonstrated that ZEA damaged the cytoskeletal structure through the induction of autophagy that leads to the alteration of cytoskeletal structure via elevated oxidative stress. Our results further showed that the autophagy was stimulated by ZEA through PI3K-AKT-mTOR and MAPK signaling pathways in TM4 cells. In addition, ZEA also induced the ER stress which was involved in the induction of the autophagy through inhibiting the ERK signal pathway to suppress the phosphorylation of mTOR. ER stress was involved in the damage of cytoskeletal structure through induction of autophagy by producing ROS. Taken together, this study revealed that ZEA altered the cytoskeletal structure via oxidative stress - autophagy- ER stress pathway in mouse TM4 Sertoli cells.

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Quinocetone triggered ER stress-induced autophagy via ATF6/DAPK1-modulated mAtg9a trafficking

Cited by 25 publications

References 40 publications

ORMDL3 Facilitates the Survival of Splenic B Cells via an ATF6α–Endoplasmic Reticulum Stress–Beclin1 Autophagy Regulatory Pathway

ORMDL3 Facilitates the Survival of Splenic B Cells via an ATF6α–Endoplasmic Reticulum Stress–Beclin1 Autophagy Regulatory Pathway

Placental DAPK1 and autophagy marker LC3B-II are dysregulated by TNF-α in a gestational age-dependent manner

Zearalenone altered the cytoskeletal structure via ER stress- autophagy- oxidative stress pathway in mouse TM4 Sertoli cells

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