Protective effects of a G. lucidum proteoglycan on INS-1 cells against IAPP-induced apoptosis via attenuating endoplasmic reticulum stress and modulating CHOP/JNK pathways

•Co-culture with FYGL decreased hIAPP induced islet cell apoptosis in vitro.•The protective mechanism of FYGL on islet cells was studied.•A new potential therapeutic method for type 2 diabetes was supported. Fudan-Yueyang-G. lucidum (FYGL) is a water-soluble macromolecular proteoglycan extracted fro...

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Published in:International journal of biological macromolecules 2018-01, Vol.106, p.893-900
Main Authors: He, Yan-Ming, Zhang, Qiang, Zheng, Min, Fan, Zhao-Hua, Li, Yun-Hao, Zhang, Dan, Zhang, Zeng, Yuan, Sha-Sha, Wang, Yan-Yan, Zhou, Ping, Yang, Hong-Jie
Format: Article
Language:English
Subjects:
Activating Transcription Factor 6 - genetics
Animals
Apoptosis
Apoptosis - drug effects
Cell Line, Tumor
eIF-2 Kinase - genetics
Endoplasmic reticulum stress
Endoplasmic Reticulum Stress - drug effects
Endoplasmic Reticulum Stress - genetics
Endoribonucleases - genetics
G. lucidum proteoglycan
Humans
Insulin-Secreting Cells - drug effects
Insulin-Secreting Cells - pathology
Insulinoma - drug therapy
Insulinoma - genetics
Insulinoma - pathology
Islet Amyloid Polypeptide - administration & dosage
MAP Kinase Signaling System - drug effects
Medicine, Chinese Traditional
Multienzyme Complexes - genetics
Protein-Serine-Threonine Kinases - genetics
Proteoglycans - administration & dosage
Proteoglycans - chemistry
Rats
Reishi - chemistry
Transcription Factor CHOP - genetics
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Summary:•Co-culture with FYGL decreased hIAPP induced islet cell apoptosis in vitro.•The protective mechanism of FYGL on islet cells was studied.•A new potential therapeutic method for type 2 diabetes was supported. Fudan-Yueyang-G. lucidum (FYGL) is a water-soluble macromolecular proteoglycan extracted from Ganoderma lucidum which has been used for health promotion for a long time in China. The aim of this study was to investigate the protective effects of FYGL on INS-1 rat insulinoma beta cells against IAPP-induced cell apoptosis, as well as the underlying mechanisms. The results showed that apoptotic cells were significantly increased when incubated with islet amyloid polypeptide (IAPP). However, cytotoxicity of IAPP was significantly attenuated by co-incubation of the cells with FYGL. The results of RT-PCR showed that mRNA expression of caspase-3, caspase-12 and C/EBP homologous protein (CHOP) in IAPP-treated cells were inhibited by FYGL. Moreover, FYGL significantly prevented the IAPP-induced abnormal expression of inositol-requiring protein-1α (IRE1α), protein kinase RNA (PKR)-like ER kinase (PERK), activating transcription factor 6 (ATF6), as well as suppressed the activation of CHOP and c-Jun N-terminal kinase (JNK). Taken together, our results suggest that FYGL protects INS-1 pancreatic beta cells against IAPP-induced apoptosis through attenuating endoplasmic reticulum stress (ERS) and modulating CHOP/JNK pathways.
ISSN:0141-8130
1879-0003
DOI:10.1016/j.ijbiomac.2017.08.089