Nesfatin-1 inhibits myocardial ischaemia/reperfusion injury through activating Akt/ERK pathway-dependent attenuation of endoplasmic reticulum stress

© 2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd..

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.

Medienart:

E-Artikel

Erscheinungsjahr:

2021

Erschienen:

2021

Enthalten in:

Zur Gesamtaufnahme - volume:25

Enthalten in:

Journal of cellular and molecular medicine - 25(2021), 11 vom: 19. Juni, Seite 5050-5059

Sprache:

Englisch

Beteiligte Personen:

Su, Rui-Ying [VerfasserIn]
Geng, Xiao-Yong [VerfasserIn]
Yang, Yang [VerfasserIn]
Yin, Hong-Shan [VerfasserIn]

Links:

Volltext

Themen:

Akt/ERK pathway
EC 2.7.11.1
EC 2.7.11.24
Endoplasmic reticulum stress
Extracellular Signal-Regulated MAP Kinases
Journal Article
Myocardial ischaemia/reperfusion injury
NUCB2/nesfatin-1
Nucb2 protein, mouse
Nucleobindins
Proto-Oncogene Proteins c-akt

Anmerkungen:

Date Completed 30.09.2021

Date Revised 30.09.2021

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1111/jcmm.16481

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM324923635