The role of mitophagy in the mechanism of genioglossal dysfunction caused by chronic intermittent hypoxia and the protec
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SLEEP BREATHING PHYSIOLOGY AND DISORDERS • ORIGINAL ARTICLE
The role of mitophagy in the mechanism of genioglossal dysfunction caused by chronic intermittent hypoxia and the protective effect of adiponectin Wenjing Wang 1 & Wenxiao Ding 2 & Hanpeng Huang 3 & Yina Zhu 1 & Ning Ding 4 & Ganzhu Feng 1 & Xilong Zhang 4 Received: 16 May 2020 / Revised: 3 September 2020 / Accepted: 2 October 2020 # Springer Nature Switzerland AG 2020
Abstract Purpose Dysfunction of the genioglossus muscle is important in the pathogenesis of obstructive sleep apnea due to chronic intermittent hypoxia (CIH). Mitochondrial impairment resulting from hypoxia is mitigated by mitophagy to avoid cell apoptosis in cardiomyocytes. This project was designed to explore the effects of CIH on mitophagy in the genioglossus muscle and the impact of adiponectin (Ad). Methods One hundred eighty male SD rats were randomly divided into 3 groups (normal control [NC], CIH, and CIH + Ad groups), with 60 rats in each group observed for 5 weeks. Comparisons of serum Ad levels, mitochondrial structure and function, mitophagy, and cell apoptosis in the genioglossus were made at different time points. Results (1) The CIH group was significantly different from the NC group as follows: During the first 3 weeks, serum Ad levels, the reactive oxygen species (ROS), relative proteins and mRNA of mitophagy, autophagy biomarker LC3-II, and autophagosomes increased, while during the last 2 weeks, most parameters decreased. (2) There was no difference among the 3 groups in mitochondrial structure and function-associated mRNA during the first 3 weeks, while damaged mitochondrial structures were growing during the last 2 weeks. Exacerbation of apoptosis was also detected in the last 2 weeks. (3) All of the damage was partially alleviated in the CIH + Ad group in contrast to CIH group at the end of this study. Conclusion Disturbances of genioglossal mitophagy could be related to damaged mitochondrial structure and function induced by CIH, which could be alleviated by supplementation of exogenous Ad via increasing mitophagy. Keywords Chronic intermittent hypoxia . Genioglossus . Mitophagy . Adiponectin . Apoptosis
Introduction Obstructive sleep apnea (OSA) is characterized by intermittent hypoxia with or without hypercapnia caused by repetitive
* Xilong Zhang [email protected] 1
Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Nanjing Medical University, 121 Jiangjiayuan Road, Nanjing 210011, China
2
Department of Respiratory Medicine, Zhongda Hospital Southeast University, 87 Dingjiaqiao, Nanjing 210009, China
3
Department of Respiratory Medicine, Affiliated Hospital of Jiangsu University, 438 Jiangfang Road, Zhenjiang 212001, China
4
Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital with Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029, China
full or partial upper airway obstruction, complicating many other comorbidities, such as hypertension, diabetes, hyperlipidemia, and
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