Irisin protects cardiomyocytes against hypoxia/reoxygenation injury via attenuating AMPK mediated endoplasmic reticulum stress

Abstract

Endoplasmic reticulum (ER) stress plays a central role in myocardial ischemia/reperfusion (I/R) injury. Irisin has been reported to have protective properties in ischemia disease. In this study, we aimed at investigating whether irisin could alleviate myocardial I/R injury by ER stress attenuation. The in vitro model of hypoxia/reoxygenation (H/R) was established, which resembles I/R in vivo. Cell viability and apoptosis were estimated. Expressions of cleaved caspase-3, cytochrome c, GRP78, pAMPK, CHOP, and eIF2α were assessed by western blot. Our results revealed that pre-treatment with irisin significantly decreased cytochrome c release from mitochondria and caspase-3 activation caused by H/R. Irsin also reduced apoptosis and increased cell viability. These effects were abolished by AMPK inhibitor compound C pre-treatment. Also, GRP78 and CHOP expressions were up-regulated in the H/R group compared to the control group; however, irisin attenuated their expression. The pAMPK level was significantly decreased compared to the control, and this effect could be partly reversed by metformin pre-treatment. These results suggest that ER stress is associated with cell viability decreasing and cardiomyocytes apoptosis induced by H/R. Irisin could efficiently protect cardiomyocytes from H/R-injury via attenuating ER stress and ER stress-induced apoptosis.

Injectable Self-Healing Oxidized Starch/Gelatin Hybrid Hydrogel for Preventing Aseptic Loosening of Bone Tissue Engineering

“…In contrast, EdU staining revealed that Ti particles markedly inhibited BMSC proliferation, which was restored by the addition of irisin (Figure S9f–g). Previous studies have reported that wear particles upregulate the expression of apoptosis-related genes such as caspase-1, caspase-3, bax, and P53, leading to apoptosis in preosteoblasts. , These compelling results suggest that irisin not only counteracts the inhibition of BMSC osteogenic differentiation caused by Ti particles but also enhances cell proliferation and reduces apoptosis, consistent with findings from other studies. − Subsequently, to further elucidate the regulatory mechanism of irisin on osteogenic differentiation, the expression levels of integrin αV, the Wnt/β-catenin signaling pathway, and genes associated with osteogenic differentiation were assessed using rt-PCR and immunofluorescence staining. As shown in Figure S10b, after 21 days of osteogenic differentiation, Ti particles suppressed the expression of osteogenic differentiation-related genes ( alp , runx2 , ocn , and sp - 7) and Wnt/β-catenin signaling pathway-related genes (β -catenin , lef- 1, and tcf- 4).…”

Irisin attenuates ventilator‐induced diaphragmatic dysfunction by inhibiting endoplasmic reticulum stress through activation of AMPK

“…Activation of AMPK can act as a physiological inhibitor of ERS and has important clinical implications for the development of therapeutic strategies for VIDD. Irisin has recently been reported to protect cardiomyocytes from hypoxia/reoxygenation injury by attenuating AMPK‐mediated ERS 28 . AMPK is a serine kinase with a wide range of biological roles.…”

“…Irisin is a newly discovered proliferator‐activated receptor‐γ coactivator‐1α (PGC‐1α)‐dependent myokine that is produced primarily in exercising muscles 27 . Irisin has anti‐inflammatory and antioxidant effects and may play an ameliorating role in acute pancreatitis, myocardial ischemia–reperfusion injury and liver fibrosis by attenuating ER stress 28,29 . However, studies of irisin in VIDD have not been reported.…”

Irisin enhances longevity by boosting SIRT1, AMPK, autophagy and telomerase

“…Also, in hypoxia/reoxygenated injury-induced endoplasmic reticulum stress irisin has a protective effect on cardiomyocytes in an AMPK-dependent manner (Ref. 65 ).…”