The role of autophagy in microwave radiation induced toxicity in iPSC-derived cardiomyocytes

Abstract

This study aims to explore the impact of microwave radiation on the electrophysiological functions of human-induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) and to focus on the critical role and underlying mechanism of autophagy in this process. The iPSC-CMs were irradiated with S-band microwaves at a power of 30 mw/cm². Through techniques such as immunofluorescence, Western blotting, electrophysiological recording, scanning electron microscopy, and transcriptomic analysis, the changes in electrophysiological indicators, ultrastructure, and autophagy levels of iPSC-CMs after microwave radiation were systematically evaluated. Further intervention with Acadesine (AICAR) was conducted to verify the role of autophagy in radiation-induced damage. After microwave radiation, iPSC-CMs exhibited significant electrophysiological dysfunction. Ultrastructural observations revealed aggravated mitochondrial damage after radiation, manifested as vacuolization, loss of cristae, and increased mitochondrial autophagy, accompanied by decreased ATP content and mitochondrial membrane potential. At the molecular level, transcriptomic analysis suggested that autophagy-related genes such as ULK1 were key regulatory nodes. After radiation, the expression of autophagy marker LC3II/I was upregulated while p62 expression was downregulated, indicating activation of the autophagic flux. Inhibition of autophagy with AICAR significantly improved the radiation-induced electrophysiological disorders. Microwave radiation can cause severe electrophysiological dysfunction in iPSC-CMs, and the mechanism is closely related to the abnormally elevated autophagy level induced by radiation. Inhibiting autophagy can effectively alleviate the electrophysiological damage caused by radiation, suggesting that targeting the autophagy pathway may be a potential strategy for protecting against the cardiotoxic effects of microwave radiation.