TUDCA protects against tunicamycin‑induced apoptosis of dorsal root ganglion neurons by suppressing activation of ER stress

Abstract

The existence of endoplasmic reticulum (ER) stress in neurodegenerative diseases has been well established. Tauroursodeoxycholic acid (TUDCA) is a bile acid taurine conjugate derived from ursodeoxycholic acid, which has been reported to exert cytoprotective effects on several types of cells by inhibiting ER stress. The present study explored the effects of TUDCA on primary cultured rat dorsal root ganglion (DRG) neurons. Cell viability and apoptosis of DRG neurons treated with TUDCA and tunicamycin were detected by CellTiter-Blue assay and TUNEL staining, respectively. The protein levels and phosphorylation of apoptosis and ERS-related signaling pathway molecules were detected by western blot, and the mRNA levels of related genes were assessed by reverse transcription-quantitative PCR. Notably, TUDCA had no significant cytotoxic effect on DRG neurons at concentrations ≤250 µM. In addition, the apoptosis induced by tunicamycin exposure was markedly suppressed by TUDCA, as indicated by the percentage of TUNEL-positive cells, the activities of caspases and the changes in expression levels of critical apoptosis factors. Furthermore, the cytotoxicity of tunicamycin in DRG neurons was accompanied by an increase in malondialdehyde (MDA) content, reactive oxygen species (ROS) and lactate dehydrogenase (LDH) production, and a decrease in glutathione (GSH) levels. The changes in oxidative stress-related factors (ROS, LDH, MDA and GSH) were reversed by TUDCA. Furthermore, as determined by western blotting, the increase in C/EBP homologous protein, glucose-regulated protein 78 and cleaved caspase-12 expression following tunicamycin treatment suggested the activation of ER stress. Downregulation of ER stress components and unfolded protein response sensors by TUDCA confirmed the implication of ER stress in the effects of TUDCA on DRG neurons. In conclusion, the present study indicated that TUDCA may protect against tunicamycin-induced DRG apoptosis by suppressing the activation of ER stress. The protective effect and the therapeutic value of TUDCA in nervous system injury require further study in animal models.

Tauroursodeoxycholic acid protects Schwann cells from high glucose–induced cytotoxicity by targeting NLRP3 to regulate cell migration and pyroptosis

“…11 TUDCA is an endogenous bile acid derived from ursodeoxycholic acid. 12,13 Evidence indicates that TUDCA plays a protective role in various diseases. [13][14][15] For example, TUDCA ameliorates glucose tolerance and insulin sensitivity in mice with Alzheimer's disease.…”

“…12,13 Evidence indicates that TUDCA plays a protective role in various diseases. [13][14][15] For example, TUDCA ameliorates glucose tolerance and insulin sensitivity in mice with Alzheimer's disease. 12 Furthermore, a previous study found that TUDCA levels were positively correlated with Parabacteroides in DPN patients, 16 implying that TUDCA might have a vital function in DPN progression.…”

“…In addition, Parabacteroides species can transform bile acids and enhance secondary bile acid content, such as tauroursodeoxycholic acid (TUDCA) 11 . TUDCA is an endogenous bile acid derived from ursodeoxycholic acid 12,13 . Evidence indicates that TUDCA plays a protective role in various diseases 13–15 .…”