1. Nesfatin‐1 inhibits myocardial ischaemia/reperfusion injury through activating Akt/ERK pathway‐dependent attenuation of endoplasmic reticulum stress
- Author
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Hong-Shan Yin, Rui-Ying Su, Yang Yang, and Xiao-Yong Geng
- Subjects
Male ,0301 basic medicine ,MAPK/ERK pathway ,Myocardial Reperfusion Injury ,Pharmacology ,Wortmannin ,Mice ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,medicine ,Animals ,Nucleobindins ,myocardial ischaemia/reperfusion injury ,Myocytes, Cardiac ,Extracellular Signal-Regulated MAP Kinases ,NUCB2/nesfatin‐1 ,Protein kinase B ,Cells, Cultured ,Cell Proliferation ,Cardioprotection ,Endoplasmic reticulum ,Original Articles ,Cell Biology ,Tunicamycin ,Endoplasmic Reticulum Stress ,medicine.disease ,Mice, Inbred C57BL ,030104 developmental biology ,Gene Expression Regulation ,chemistry ,030220 oncology & carcinogenesis ,Unfolded protein response ,Molecular Medicine ,Original Article ,Akt/ERK pathway ,Proto-Oncogene Proteins c-akt ,Reperfusion injury - Abstract
Nesfatin‐1 (encoded by NUCB2) is a cardiac peptide possessing protective activities against myocardial ischaemia/reperfusion (MI/R) injury. However, the regulation of NUCB2/nesfatin‐1 and the molecular mechanisms underlying its roles in MI/R injury are not clear. Here, by investigating a mouse MI/R injury model developed with transient myocardial ischaemia followed by reperfusion, we found that the levels of NUCB2 transcript and nesfatin‐1 amount in the heart were both decreased, suggesting a transcriptional repression of NUCB2/nesfatin‐1 in response to MI/R injury. Moreover, cardiac nesfatin‐1 restoration reduced infarct size, troponin T (cTnT) level and myocardial apoptosis, supporting its cardioprotection against MI/R injury in vivo. Mechanistically, the Akt/ERK pathway was activated, and in contrast, endoplasmic reticulum (ER) stress was attenuated by nesfatin‐1 following MI/R injury. In an in vitro system, similar results were obtained in nesfatin‐1‐treated H9c2 cardiomyocytes with hypoxia/reoxygenation (H/R) injury. More importantly, the treatment of wortmannin, an inhibitor of Akt/ERK pathway, abrogated nesfatin‐1 effects on attenuating ER stress and H/R injury in H9c2 cells. Furthermore, nesfatin‐1‐mediated protection against H/R injury also vanished in the presence of tunicamycin (TM), an ER stress inducer. Lastly, Akt/ERK inhibition reversed nesfatin‐1 effects on mouse ER stress and MI/R injury in vivo. Taken together, these findings demonstrate that NUCB2/nesfatin‐1 inhibits MI/R injury through attenuating ER stress, which relies on Akt/ERK pathway activation. Hence, our study provides a molecular basis for understanding how NUCB2/nesfatin‐1 reduces MI/R injury.
- Published
- 2021