Glucagon-like peptide-1 attenuates endoplasmic reticulum stress–induced apoptosis in H9c2 cardiomyocytes during hypoxia/reoxygenation through the GLP-1R/PI3K/Akt pathways

Autor: Jun Zhang, Xiang Gu, Wenyin Huang, Gaopeng Guan, Shengyuan Liu, Ying Gong
Rok vydání: 2019
Předmět:
0301 basic medicine
endocrine system
medicine.medical_specialty
Apoptosis
Myocardial Reperfusion Injury
030204 cardiovascular system & hematology
Glucagon-Like Peptide-1 Receptor
Phosphatidylinositol 3-Kinases
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Downregulation and upregulation
Glucagon-Like Peptide 1
Internal medicine
medicine
Animals
Myocytes
Cardiac
LY294002
Protein kinase B
Cells
Cultured
PI3K/AKT/mTOR pathway
Pharmacology
Akt/PKB signaling pathway
Endoplasmic reticulum
digestive
oral
and skin physiology
General Medicine
Endoplasmic Reticulum Stress
Rats
030104 developmental biology
Endocrinology
chemistry
Unfolded protein response
Signal transduction
Proto-Oncogene Proteins c-akt
hormones
hormone substitutes
and hormone antagonists
Signal Transduction
Zdroj: Naunyn-Schmiedeberg's Archives of Pharmacology. 392:715-722
ISSN: 1432-1912
0028-1298
DOI: 10.1007/s00210-019-01625-2
Popis: Endoplasmic reticulum (ER) stress-induced apoptosis is a major cause of myocardial ischemia/reperfusion (I/R) injury. Emerging evidence indicates that glucagon-like peptide-1 (GLP-1) has potential cardioprotective effects. However, the precise mechanisms underlying the involvement of GLP-1 in I/R injury remain largely unknown. In the present study, we aimed to determine whether GLP-1 attenuates hypoxia/reoxygenation (H/R) injury in cardiomyocytes and to further elucidate the underlying signaling pathway. The results indicate that GLP-1 reversed the increased apoptotic ratio, the increased lactate dehydrogenase (LDH) levels, the reduced cell viability, the increased Caspase-3 activity, and the increased Bax/Bcl-2 ratio caused by H/R. Importantly, GLP-1 significantly decreased the expression of H/R-induced ER stress proteins (GRP78, CHOP) and Caspase-12. In addition, we found that GLP-1 increased the expression of p-Akt in H9c2 cells with H/R injuries, and that the protective action of GLP-1 against H/R-induced injury was blocked by the GLP-1 receptor (GLP-1R) inhibitor Exendin9-39 and the PI3K inhibitor LY294002. Exendin9-39 and LY294002 also blocked the downregulation of ER stress protein expression by GLP-1, after H/R injury. Therefore, we have shown that GLP-1 exerts its cardioprotective effects by alleviating ER stress-induced apoptosis due to H/R injury and that these effects are most likely associated with the activation of GLP-1R/PI3K/Akt signaling pathway.
Databáze: OpenAIRE
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