Adiponectin may inhibit chronic intermittent hypoxia-induced endoplasmic reticulum stress and cell apoptosis in genioglossus

Abstract

Introduction Adiponectin may inhibit chronic intermittent hypoxia-induced endoplasmic reticulum stress and cell apoptosis in genioglossus Background Adiponectin is a potent protective molecule against injury caused by chronic intermittent hypoxia (CIH). However, the protective mechanism is not well elucidated. Cell apoptosis was remarkable in genioglossus of rats undergoing CIH. Enhanced endoplasmic reticulum (ER) stress has been recognized as the precursor of acceleration of cell apoptosis. Objective The present study aims to investigate the effects of CIH and adoponectin supplement on ER stress and cell apoptosis in genioglossus of rats. Materials and methods 30 male Wistar rats were randomly divided into three groups: normal control group (group A), CIH group (group B) and CIH+Ad group (group C) with 10 rats in each. Rats in group A were kept breathing normal air, while rats in both group B and group C received same CIH environment (CIH 8 hr/day for successive 5 weeks). However, rats in group C was given intravenous Ad supplement at the dosage of 100 ∣ μg/kg, twice a week for sucessive 5 weeks. At the end of experiment (day 35), the expression of glucose-regulated protein 78(GRP78), P38, c-Jun NH-terminal kinase (JNK) and C/EBP homologous protein (CHOP) proteins of genioglossus were tested with western blot assay. In addition, the cell apoptosis of genioglossus in each group was measured through TUNEL and Annexin V/PI staining. Results Compared with control group, in CIH group the P38 was significantly activated, the expression of GRP78 and CHOP proteins of genioglossus were significantly upregulated, and the rate of cell apoptosis was significantly elevated (all P 0.01). However, compared with CIH group, in group C the activation of P38 was partially inhibited, the expression of GRP78 and CHOP proteins was significantly weakened, and the rate of cell apoptosis was remarkably lower (all P 0.05). There was no significant difference of JNK expression of genioglossus among three groups (P > 0.05). Conclusion Conclusions CIH could induce ER stress and significantly elevate the rate of cell apoptosis through ativation of P38-CHOP pathway in genioglossus of rats submitted to CIH. Supplement of extrinsic adiponectin could attenuate excessive ER stress, inhibit activation of P38-CHOP pathway, and thus further reduce the rate of cell apoptosis induced by CIH in genioglossus. Acknowledgements Thanks to the support from the Department of pathophysiology, Nanjing Medical University for prividing this study with CIH instrument.