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The Chondroprotective Role of TMF in PGE2-Induced Apoptosis Associating with Endoplasmic Reticulum Stress.

ABSTRACT: Endoplasmic reticulum stress (ERS) has been demonstrated to exhibit a critical role in osteoarthritic chondrocytes. Whether 5,7,3',4'-tetramethoxyflavone (TMF) plays the chondroprotective role in inhibition of PGE2-induced chondrocytes apoptosis associating with ERS has not been reported. To investigate this, the activation of PERK, ATF6, and IRE1 signaling pathways in ERS in chondrocytes pretreated with PGE2 was studied. By treatment with PGE2, the chondrocytes apoptosis was significantly increased, the proapoptotic CHOP and JNK were upregulated, the prosurvival GRP78 and XBP1 were downregulated, and GSK-3? was also upregulated. However, TMF exhibited the effectively protective functions via counteracting these detrimental effects of PGE2. Finally, the inflammatory cytokine PGE2 can activate ERS signaling and promote chondrocytes apoptosis, which might be associated with upregulation of GSK-3?. TMF exhibits a chondroprotective role in inhibiting PGE2-induced ERS and GSK-3?.

SUBMITTER: Yang J

PROVIDER: S-EPMC4576019 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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The Chondroprotective Role of TMF in PGE2-Induced Apoptosis Associating with Endoplasmic Reticulum Stress.

Yang Jianqiong J Liu Haiqing H Li Linfu L Liu Hai H Shi Weimei W Wu Longhuo L

Evidence-based complementary and alternative medicine : eCAM 20150907

Endoplasmic reticulum stress (ERS) has been demonstrated to exhibit a critical role in osteoarthritic chondrocytes. Whether 5,7,3',4'-tetramethoxyflavone (TMF) plays the chondroprotective role in inhibition of PGE2-induced chondrocytes apoptosis associating with ERS has not been reported. To investigate this, the activation of PERK, ATF6, and IRE1 signaling pathways in ERS in chondrocytes pretreated with PGE2 was studied. By treatment with PGE2, the chondrocytes apoptosis was significantly incre ...[more]

PMID: 26435723

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Project description:Endoplasmic reticulum (ER) stress and apoptotic cell death play an important role in the pathogenesis and perpetuation of inflammatory bowel disease (IBD). We aimed to explore the potential of glutamine to reduce ER stress and apoptosis in a rat model of experimental IBD. Colitis was induced in male Wistar rats by intracolonic administration of 30 mg of 2,4,6-trinitrobenzene sulfonic acid (TNBS). Glutamine (25 mg/dL) was given by rectal route daily for 2 d or 7 d. Both oxidative stress (TBARS concentration and oxidised/reduced glutathione ratio) and ER stress markers (CHOP, BiP, calpain-1 and caspase-12 expression) increased significantly within 48 h of TNBS instillation, and glutamine attenuated the extent of the changes. Glutamine also inhibited the significant increases of ATF6, ATF4 and spliced XBP-1 mRNA levels induced by TNBS instillation. TNBS-colitis resulted in a significant increase in p53 and cytochrome c expression, and a reduced Bcl-xL expression and Bax/Bcl-2 ratio. These effects were significantly inhibited by glutamine. Treatment with the amino acid also resulted in significant decreases of caspase-9, caspase-8 and caspase-3 activities. Double immunofluorescence staining showed co-localization of CHOP and cleaved caspase-3 in colon sections. Phospho-JNK and PARP-1 expression was also significantly higher in TNBS-treated rats, and treatment with glutamine significantly decreased JNK phosphorylation and PARP-1 proteolysis. To directly address the effect of glutamine on ER stress and apoptosis in epithelial cells, the ER stress inducers brefeldin A and tunicamycin were added to Caco-2 cells that were treated with glutamine (5 mM and 10 mM). The significant enhancement in PERK, ATF6 phosphorylated IRE1, BiP and cleaved caspase-3 expression induced by brefeldin A and tunicamycin was partly prevented by glutamine. Data obtained indicated that modulation of ER stress signalling and anti-apoptotic effects contribute to protection by glutamine against damage in TNBS-induced colitis.

Dataset Information

The Chondroprotective Role of TMF in PGE2-Induced Apoptosis Associating with Endoplasmic Reticulum Stress.

Publications

The Chondroprotective Role of TMF in PGE2-Induced Apoptosis Associating with Endoplasmic Reticulum Stress.

Similar Datasets

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