Oxidative and endoplasmic reticulum stresses are involved in palmitic acid-induced H9c2 cell apoptosis

Yang, Lei; Guan, Gaopeng; Lei, Lanjie; Liu, Jianyun; Cao, Lingling; Wang, Xiangguo

doi:10.1042/bsr20190225

Cited by 46 publications

(42 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Under these conditions, ER load is ameliorated by following three methods: (1) a reduction in the entry of newly synthesized proteins into the ER through attenuating protein translation; (2) an increase in the protein-folding capacity by up-regulating ER gene expression; (3) the degradation of misfolded and unfolded proteins through ER-associated degradation (ERAD) and lysosome-mediated autophagy [18, 22, 23]. ER stress occurs widely in several physiological and pathological processes, including development, cell apoptosis, autophagy, and metabolic diseases [18, 24]. The role of ER stress in immune response [25, 26], inflammation [25], and female reproduction [27,28,29,30,31] have also been reported previously.…”

mentioning

confidence: 99%

Role of endoplasmic reticulum stress in lipopolysaccharide-inhibited mouse granulosa cell estradiol production

Lei

Zhao

et al. 2019

J. Reprod. Dev.

Self Cite

View full text Add to dashboard Cite

The decrease in the level of estradiol (E 2) in granulosa cells caused by lipopolysaccharide (LPS) is one of the major causes of infertility underlying postpartum uterine infections; the precise molecular mechanism of which remains elusive. This study investigated the role of endoplasmic reticulum (ER) stress in LPS-induced E 2 decrease in mouse granulosa cells. Our results showed that LPS increased the pro-inflammatory cytokines [(interleukin (IL)-1β, IL-6, IL-8, and tumor necrosis factor (TNF)-α)], activated ER stress marker protein expression [(glucose-regulated protein 78 (GRP78) and CCAAT/enhancerbinding protein homologous protein (CHOP)], and decreased cytochrome P450 family 19 subfamily A member 1 (Cyp19a1) expression and E 2 production. Moreover, inhibition of ER stress by 4-phenylbutyrate (4-PBA) attenuated thapsigargin-(TG, ER stress agonist) or LPS-induced reduction of Cyp19a1 and E 2 , pro-inflammatory cytokines expression (IL-1β, IL-6, IL-8, and TNF-α), and the expression of CHOP and GRP78. Additionally, inhibition of toll-like receptor 4 (TLR4) by resatorvid (TAK-242) reversed the inhibitory effects of LPS on Cyp19a1 expression and E 2 production, activation of GRP78 and CHOP, and expression of IL-1β, IL-6, IL-8, and TNF-α. In summary, our study suggests that ER stress is involved in LPS-inhibited E 2 production in mouse granulosa cells.

show abstract

mentioning

confidence: 99%

Role of endoplasmic reticulum stress in lipopolysaccharide-inhibited mouse granulosa cell estradiol production

Lei

Zhao

et al. 2019

J. Reprod. Dev.

Self Cite

View full text Add to dashboard Cite

show abstract

“…Similar to PERK, excessive ERS can lead to the autophosphorylation of IRE1, which then initiate the downstream ASK1-JNK pathway by its phosphokinase activity. As apoptotic factors, the continued expression of JNK and CHOP can cause body injury by blocking the cell cycle and inducing apoptosis [ 26 – 29 ]. In the present study, after treated with 100 μ M DEX for 24 h, the results showed that the treatment of high-concentration GC leaded to the increased expression of ERS-related proteins GRP78, ATF4, CHOP, ASK1, and JNK in PC12 cells and increased phosphorylation levels of PERK and IRE1.…”

Section: Discussionmentioning

confidence: 99%

Endoplasmic Reticulum Stress Is Involved in Glucocorticoid-Induced Apoptosis in PC12 Cells

Shi

Zuo

et al. 2021

Analytical Cellular Pathology

View full text Add to dashboard Cite

Objective. The present study selected PC12 cells to construct a neuronal injury model induced by glucocorticoids (GC) in vitro, aiming to explore whether the endoplasmic reticulum stress (ERS) PKR-like endoplasmic reticulum kinase (PERK)-activating transcription factor 4 (ATF4)-C/EBP-homologous protein (CHOP) and inositol requirement 1 (IRE1)-apoptosis signal regulating kinase 1 (ASK1)-C-Jun amino-terminal kinase (JNK) signaling pathways are associated with the neuronal injury process induced by GC and provide morphological evidence. Methods. Cell models with different doses and different durations of GC exposure were established. The viability of PC12 cells was detected by the CCK-8 assay, and the apoptosis rate of PC12 cells was detected by the flow cytometry assay. The expression of microtubule-associated protein 2 (Map2); glucocorticoids receptor (GR); cellular oncogene fos (C-fos); and ERS-related proteins, glucose-regulated protein 78 (GRP78), p-PERK, p-IRE1, ATF4, ASK1, JNK, and CHOP, was observed by immunofluorescence staining. Results. The results of immunofluorescence staining showed that PC12 cells abundantly expressed Map2 and GR. The CCK-8 assay revealed that high-concentration GC exposure significantly inhibited the cell viability of PC12 cells. The flow cytometry assay indicated that high-concentration GC exposure significantly increased the apoptosis rate of PC12 cells. Immunofluorescence staining showed that GC exposure significantly increased the expression of C-fos, GRP78, p-PERK, p-IRE1, ATF4, ASK1, JNK, and CHOP. Treatment with ERS inhibitor 4-phenylbutyric acid (4-PBA) and GR inhibitor RU38486 attenuated related damage and downregulated the expression of the abovementioned proteins. Conclusion. High-concentration GC exposure can significantly inhibit the viability of PC12 cells and induce apoptosis. PERK-ATF4-CHOP and IRE1-ASK1-JNK pathways are involved in the above damage process.

show abstract

“…This subsequently promotes mitochondrial ca 2+ overload, which triggers cell apoptosis by opening the mitochondrial permeability transition pore (43). Oxidative stress promotes ERS, and persistent ERS has been observed to promote mitochondrial dysfunction, which in turn induces oxidative stress (44). As previously mentioned, ERO1α is strongly associated with the generation of ROS, and it has been demonstrated that due to excessive oxidation, ERO1α enhances inositol triphosphate receptor (IP3R) activity, and promotes IP3R-mediated Ca 2+ release and transfer to the mitochondria, facilitating apoptosis (45,46).…”

Section: Discussionmentioning

confidence: 99%

Role of endoplasmic reticulum oxidase 1α in H9C2 cardiomyocytes following hypoxia/reoxygenation injury

Lai

Liu

et al. 2020

Mol Med Rep

View full text Add to dashboard Cite

endoplasmic reticulum (er) oxidase 1α (ero1α) is a glycosylated flavoenzyme that is located on the luminal side of the ER membrane, which serves an important role in catalyzing the formation of protein disulfide bonds and ER redox homeostasis. However, the role of ERO1α in myocardial hypoxia/reoxygenation (H/R) injury remains largely unknown. In the present study, ERO1α expression levels in H9C2 cardiomyocytes increased following H/R, reaching their highest levels following 3 h of hypoxia and 6 h of reoxygenation. In addition, H/R induced apoptosis, and significantly increased expression levels of ER stress (ERS) markers 78 kda glucose-regulated protein and c/EBP homologous protein. Moreover, the genetic knockdown of ERO1α using short hairpin RNA suppressed cell apoptosis, caspase-3 activity, expression levels of cleaved caspase-12 and cytochrome c in the cytoplasm. Overall, this suggested that ERO1α knockdown may protect against H/r injury. The ERS activator tunicamycin (TM) was used to counteract the ERO1α-induced reduction in ERS; however, the percentage of apoptotic cells and the level of mitochondrial damage did not change. In conclusion, the results from the present study suggested that ERO1α knockdown may protect H9C2 cardiomyocytes from H/R injury through inhibiting intracellular roS production and increasing intracellular levels of Ca 2+ , suggesting that ERO1α may serve an important role in H/R.

show abstract

Oxidative and endoplasmic reticulum stresses are involved in palmitic acid-induced H9c2 cell apoptosis

Cited by 46 publications

References 24 publications

Role of endoplasmic reticulum stress in lipopolysaccharide-inhibited mouse granulosa cell estradiol production

Role of endoplasmic reticulum stress in lipopolysaccharide-inhibited mouse granulosa cell estradiol production

Endoplasmic Reticulum Stress Is Involved in Glucocorticoid-Induced Apoptosis in PC12 Cells

Role of endoplasmic reticulum oxidase 1α in H9C2 cardiomyocytes following hypoxia/reoxygenation injury

Contact Info

Product

Resources

About