[Ginsenoside Rg_1 ameliorates OGD/R-induced PC12 cell injury by inhibiting autography via IRE1-JNK-CHOP pathway].

Publisher: Zhongguo yao xue hui : Zhongguo Zhong yi yan jiu yuan Zhong yao yan jiu suo Country of Publication: China NLM ID: 8913656 Publication Model: Print Cited Medium: Print ISSN: 1001-5302 (Print) Linking ISSN: 10015302 NLM ISO Abbreviation: Zhongguo Zhong Yao Za Zhi Subsets: MEDLINE

Publication: Beijing : Zhongguo yao xue hui : Zhongguo Zhong yi yan jiu yuan Zhong yao yan jiu suo
Original Publication: [Beijing] : Zhongguo yao xue hui : [Zhongguo Zhong yi yan jiu yuan Zhong yao yan jiu suo, 1989-

Transcription Factor CHOP*/metabolism ; Transcription Factor CHOP*/genetics ; Glucose*/metabolism ; Ginsenosides*/pharmacology ; Protein Serine-Threonine Kinases*/metabolism ; Protein Serine-Threonine Kinases*/genetics ; Apoptosis*/drug effects; Animals ; Rats ; PC12 Cells ; Signal Transduction/drug effects ; Autophagy/drug effects ; Endoribonucleases/metabolism ; Endoribonucleases/genetics ; JNK Mitogen-Activated Protein Kinases/metabolism ; JNK Mitogen-Activated Protein Kinases/genetics ; Oxygen/metabolism ; Endoplasmic Reticulum Stress/drug effects ; Multienzyme Complexes

This study investigated the protective effect of ginsenoside Rg_1(GRg_1) on oxygen and glucose deprivation/reoxygenation(OGD/R)-injured rat adrenal pheochromocytoma(PC12) cells and whether the underlying mechanism was related to the regulation of inositol-requiring enzyme 1(IRE1)-c-Jun N-terminal kinase(JNK)-C/EBP homologous protein(CHOP) signaling pathway. An OGD/R model was established in PC12 cells, and PC12 cells were randomly classified into control, model, OGD/R+GRg_1(0.1, 1, 10 μmol·L~(-1)), OGD/R+GRg_1+rapamycin(autophagy agonist), OGD/R+GRg_1+3-methyladenine(3-MA,autophagy inhibitor), OGD/R+GRg_1+tunicamycin(endoplasmic reticulum stress agonist), OGD/R+GRg_1+4-phenylbutyric acid(4-PBA, endoplasmic reticulum stress inhibitor), and OGD/R+GRg_1+3,5-dibromosalicylaldehyde(DBSA, IRE1 inhibitor) groups. Except the control group, the other groups were subjected to OGD/R treatment, i.e., oxygen and glucose deprivation for 6 h followed by reoxygenation for 6 h. Cell viability was detected by the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl tetrazolium bromide(MTT) assay. Apoptosis was detected by Hoechst 33342 staining, and the fluorescence intensity of autophagosomes by the monodansylcadaverine(MDC) assay. Western blot was employed to determine the expression of autophagy-related proteins(Beclin1, LC3-Ⅱ, and p62) and the pathway-related proteins [IRE1, p-IRE1, JNK, p-JNK, glucose-regulated protein 78(GRP78), and CHOP]. The results showed that GRg_1 dose-dependently increased the viability of PC12 cells and down-regulated the expression of Beclin1, LC3-Ⅱ, p-IRE1, p-JNK, GRP78, and CHOP, compared with the model group. Furthermore, GRg_1 decreased the apoptosis rate and MDC fluorescence intensity and up-regulated the expression of p62 protein. Compared with the OGD/R+GRg_1(10 μmol·L~(-1)) group, OGD/R+GRg_1+rapamycin and OGD/R+GRg_1+tunicamycin groups showed increased apoptosis rate and MDC fluorescence intensity, up-regulated protein levels of Beclin1, LC3-Ⅱ, p-IRE1, p-JNK, GRP78, and CHOP, decreased relative cell survival rate, and down-regulated protein level of p62. The 3-MA, 4-PBA, and DBSA groups exerted the opposite effects. Taken together, GRg_1 may ameliorate OGD/R-induced PC12 cell injury by inhibiting autophagy via the IRE1-JNK-CHOP pathway.

Keywords: IRE1-JNK-CHOP; autophagy; endoplasmic reticulum stress; ginsenoside Rg_1(GRg_1); oxygen and glucose deprivation/reoxygenation(OGD/R)

147336-12-7 (Transcription Factor CHOP)
IY9XDZ35W2 (Glucose)
0 (Ginsenosides)
EC 2.7.11.1 (Protein Serine-Threonine Kinases)
PJ788634QY (ginsenoside Rg1)
EC 3.1.- (Endoribonucleases)
0 (Ern1 protein, rat)
EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases)
S88TT14065 (Oxygen)
0 (Multienzyme Complexes)

Date Created: 20240530 Date Completed: 20240530 Latest Revision: 20240614

20240615

10.19540/j.cnki.cjcmm.20231128.405

38812175