Tauroursodeoxycholic acid alleviates secondary injury in the spinal cord via up-regulation of CIBZ gene

Abstract

Spinal cord injury (SCI) is generally divided into primary and secondary injuries, and apoptosis is an important event of the secondary injury. As an endogenous bile acid and recognized endoplasmic reticulum (ER) stress inhibitor, tauroursodeoxycholic acid (TUDCA) administration has been reported to have a potentially therapeutic effect on neurodegenerative diseases, but its real mechanism is still unclear. In this study, we evaluated whether TUDCA could alleviate traumatic damage of the spinal cord and improve locomotion function in a mouse model of SCI. Traumatic SCI mice were intraperitoneally injected with TUDCA, and the effects were evaluated based on motor function assessment, histopathology, apoptosis detection, qRT-PCR, and western blot at different time periods. TUDCA administration can improve motor function and reduce secondary injury and lesion area after SCI. Furthermore, the apoptotic ratios were significantly reduced; Grp78, Erdj4, and CHOP were attenuated by the treatment. Unexpectedly, the levels of CIBZ, a novel therapeutic target for SCI, were specifically up-regulated. Taken together, it is suggested that TUDCA effectively suppressed ER stress through targeted up-regulation of CIBZ. This study also provides a new strategy for relieving secondary damage by inhibiting apoptosis in the early treatment of spinal cord injury.

Ketogenic Diet-mediated Steroid Metabolism Reprogramming Improves the Immune Microenvironment and Myelin Growth of Spinal Cord Injury Rats Through Gene Analysis and Co-expression Network Analysis

“…Our research studies have shown that KD reduces or inhibits neutrophils in the plasma of SCI rats and inhibits the classic NF-κB pro-in ammatory signalling pathway at the injury site, which corresponds to the results of this study [17]. Steroid synthesis is also closely related to SCI neuroin ammation, and steroid synthesis hormones [42], oestrogen [43][44], saponin [45], tauroursodeoxycholic acid [46] and other steroid components in the spinal cord injury all have anti-in ammatory properties. Fig.…”

Anticancer effect of caudatin in diethylnitrosamine‑induced hepatocarcinogenesis in rats

“…XBP1 mrna further splices into XBP1s, which participates in the protein folding of erdJ4. in addition, GrP78 overexpression coupled with erdJ4 shrinks the induction of cHoP in erS and decreases erS-induced apoptosis (58).…”

Transcriptional network constituted of CBP, Ku70, NOX2, and BAX prevents the cell death of necrosis, paraptosis, and apoptosis in human melanoma

“…The chromatin condensation was analyzed using DAPI staining 43 , specifically, 1 × 10 5 melanoma A375 cells were seeded into a well in a six-well plate placed with a sterilized glass coverslip in the well, and cultivated in the presence of 5% CO 2 gas at 37 °C for 24 h. The cells were subdivided into control group, CBP siRNA group (with 70% efficiency of CBP mRNA depletion), Ku70 siRNA group (with 70% efficiency of Ku70 mRNA depletion), CBP–Ku70 siRNA co-transfection group (with 60% efficiencies of CBP mRNA and Ku70 mRNA depletion, respectively), and NC siRNA group. The cells of each group were processed using 1 ml fix solution containing 4% paraformaldehyde (Beyotime Biotechnology, Nantong, China) for 10 min, when the cultivations were at 0, 8, 12, 16, 20, and 24 h, respectively.…”