Lycium barbarum polysaccharide prevents cisplatin-induced MLTC-1 cell apoptosis and autophagy via regulating endoplasmic reticulum stress pathway

Fenglian Yang,1 Yuxia Wei,2 Biyun Liao,2 Guijiang Wei,2 Haimei Qin,2 Xiaoxia Pang,2 Junli Wang2 1Department of Reproductive Medicine, Youjiang Medical College for Nationalities, Baise, Guangxi 533000, China; 2Department of Reproductive Medicine, Affiliated Hospital of Youjiang Medical College for Nationalities, Baise, Guangxi 533000, China Background: Lycium barbarum polysaccharide (LBP) has been reported to contribute to the recovery of male hypogonadism and infertility. Aim: The aim of current study was to investigate the underlying mechanisms of LBP on male infertility recovery. Methods: Recently, it is reported that cell apoptosis mediated by endoplasmic reticulum stress (ERS) was distinguished from that mediated by death reporters and mitochondria pathway, which could induce cell apoptosis independently. The possible signaling mechanisms were investigated using diversified molecular biology techniques, such as flow cytometry, western blotting, and immunofluorescence. Results: In this study, we found that LBP protected Leydig MLTC-1 cells against cisplatin (DDP) by regulating ERS-mediated signal pathway, which was evidenced by downregulation of phosphorylation PERK, phosphorylation of eukaryotic translation-initiation factor 2α and activating transcription factor 4. Meanwhile, LBP decreased DDP-induced MLTC-1 cell apoptosis via reducing ERS apoptosis-relative proteins caspase 3, caspase 7, and caspase 12. In addition, the result of monodansylcadaverine staining indicated that LBP significantly inhibited DDP-induced autophagosome formation in MLTC-1 cells. Moreover, immunofluorescences and Western blot assays demonstrated that LBP reversed DDP-induced LC3II and Atg5 upregulation in MLTC-1 cells. Finally, the data of enzyme-linked immunosorbent assay showed that LBP markedly recovered MLTC-1 cells testosterone level even in the presence of DDP. Conclusion: Thus, we suggest that LBP protected MLTC-1 cells against DDP via regulation of ERS-mediated apoptosis and autophagy. Keywords: L. barbarum polysaccharide, endoplasmic reticulum stress, hypogonadism, DDP, MLTC-1 cell, autophagy, apoptosi