| First Author | Zhao J | Year | 2023 |
| Journal | Redox Biol | Volume | 59 |
| Pages | 102594 | PubMed ID | 36603528 |
| Mgi Jnum | J:351491 | Mgi Id | MGI:7424294 |
| Doi | 10.1016/j.redox.2022.102594 | Citation | Zhao J, et al. (2023) Diminished alpha7 nicotinic acetylcholine receptor (alpha7nAChR) rescues amyloid-beta induced atrial remodeling by oxi-CaMKII/MAPK/AP-1 axis-mediated mitochondrial oxidative stress. Redox Biol 59:102594 |
| abstractText | The potential coexistence of Alzheimer's disease (AD) and atrial fibrillation (AF) is increasingly common as aging-related diseases. However, little is known about mechanisms responsible for atrial remodeling in AD pathogenesis. alpha7 nicotinic acetylcholine receptors (alpha7nAChR) has been shown to have profound effects on mitochondrial oxidative stress in both organ diseases. Here, we investigate the role of alpha7nAChR in mediating the effects of amyloid-beta (Abeta) in cultured mouse atrial cardiomyocytes (HL-1 cells) and AD model mice (APP/PS1). In vitro, apoptosis, oxidative stress and mitochondrial dysfunction induced by Abeta long-term (72h) in HL-1 cells were prevented by alpha-Bungarotoxin(alpha-BTX), an antagonist of alpha7nAChR. This cardioprotective effect was due to reinstating Ca(2+) mishandling by decreasing the activation of CaMKII and MAPK signaling pathway, especially the oxidation of CaMKII (oxi-CaMKII). In vivo studies demonstrated that targeting knockdown of alpha7nAChR in cardiomyocytes could ameliorate AF progression in late-stage (12 months) APP/PS1 mice. Moreover, alpha7nAChR deficiency in cardiomyocytes attenuated APP/PS1-mutant induced atrial remodeling characterized by reducing fibrosis, atrial dilation, conduction dysfunction, and inflammatory mediator activities via suppressing oxi-CaMKII/MAPK/AP-1. Taken together, our findings suggest that diminished alpha7nAChR could rescue Abeta-induced atrial remodeling through oxi-CaMKII/MAPK/AP-1-mediated mitochondrial oxidative stress in atrial cells and AD mice. |
