[Retracted] Irisin Attenuates Oxidative Stress, Mitochondrial Dysfunction, and Apoptosis in the H9C2 Cellular Model of Septic Cardiomyopathy through Augmenting Fundc1‐Dependent Mitophagy

Abstract

In the present study, we used lipopolysaccharide- (LPS-) stimulated H9C2 cardiomyocytes to investigate whether irisin treatment attenuates septic cardiomyopathy via Fundc1-related mitophagy. Fundc1 levels and mitophagy were significantly reduced in LPS-stimulated H9C2 cardiomyocytes but were significantly increased by irisin treatment. Irisin significantly increased ATP production and the activities of mitochondrial complexes I and III in the LPS-stimulated cardiomyocytes. Irisin also improved glucose metabolism and significantly reduced LPS-induced levels of reactive oxygen species by increasing the activities of antioxidant enzymes, glutathione peroxidase (GPX), and superoxide dismutase (SOD), as well as levels of reduced glutathione (GSH). TUNEL assays showed that irisin significantly reduced LPS-stimulated cardiomyocyte apoptosis by suppressing the activation of caspase-3 and caspase-9. However, the beneficial effects of irisin on oxidative stress, mitochondrial metabolism, and viability of LPS-stimulated H9C2 cardiomyocytes were abolished by silencing Fundc1. These results demonstrate that irisin abrogates mitochondrial dysfunction, oxidative stress, and apoptosis through Fundc1-related mitophagy in LPS-stimulated H9C2 cardiomyocytes. This suggests irisin is a potentially useful treatment for septic cardiomyopathy, though further investigations are necessary to confirm our findings.

Melatonin Improved the Survival of Multi-Territory Perforator Flaps by Promoting Angiogenesis and Inhibiting Apoptosis via the NRF2/FUNDC1 Axis

“…Interestingly, Wang et al ( Wang et al, 2021 ) proposed that FUNDC1 was an integral mitochondrial outer-membrane protein that could increase the expression of VEGF and promote endothelial cell angiogenesis. Similarly, FUNDC1 not only alleviates ischemia–reperfusion injury but also inhibits apoptosis ( Wang et al, 2018 ; Jiang X. et al, 2021 ; Cai et al, 2021 ; Li et al, 2021 ). In our study, we observed that MLT treatment reduced the area of ischemic necrosis of the flap.…”

Protective Effect of Natural Medicinal Plants on Cardiomyocyte Injury in Heart Failure: Targeting the Dysregulation of Mitochondrial Homeostasis and Mitophagy

“…However, after FUNDC1 knockdown in cardiomyocytes, the regulatory mechanisms of irisin on oxidative stress, mitochondrial energy metabolism, and mitophagy in cardiomyocytes were eliminated, and the caspase-3/caspase-9-mediated apoptosis was suppressed. These results suggest that the regulatory effects of irisin on cardiomyocyte activity and mitochondrial energy metabolism are mediated by FUNDC1 [ 164 ].…”

Irisin is an Effector Molecule in Exercise Rehabilitation Following Myocardial Infarction (Review)

“…Jiang (2021) (Jiang et al, 2021) Lipopolysaccharide-stimulated cardiomyocytes ↓Bax, caspase-3 and Fundc1…”

“…Irisin is mainly secreted in skeletal ( Boström et al, 2012 ) and cardiac muscle tissue ( Aydin et al, 2014 ), and is implicated in modulation of mitochondrial function and energy balance ( Ouyang et al, 2020 ; Xin et al, 2020 ) lipid and glucose metabolism ( Perakakis et al, 2017 ; Wang et al, 2020 ), and amelioration of impaired cardiac function in some metabolic disorders ( Wang et al, 2017 ; Jiang et al, 2021 ). Previous findings show that circulating irisin level is lower in patients with chronic heart failure ( Silvestrini et al, 2019 ), middle cerebral artery occlusion (MCAO) patients ( Li et al, 2017 ), and subjects with Alzheimer disease (AD) ( Kim et al, 2018 ) compared with normal subjects.…”