Septin4 regulates endoplasmic reticulum stress and apoptosis in melatonin‑induced osteoblasts

Abstract

idiopathic scoliosis (iS) is a spinal 3-dimensional deformity with an unknown cause. Melatonin is secreted by the pineal body and contributes to the occurrence and progression of iS. in our previous preliminary study, it was reported that high concentrations of melatonin can induce osteoblast apoptosis, thus acting as an iS treatment, but the mechanism of action is unknown. Therefore, the present study was performed to further investigate the possible mechanism underlying the efficacy of melatonin as a treatment for IS. The present results indicated that high concentrations of melatonin mediate endoplasmic reticulum stress (erS)-induced apoptosis in hFOB 1.19 cells, and this resulted in a significant and dose-dependent increase in the expression of Septin4, as well as the expression levels of glucose-regulated protein (GrP)78, GrP94 and cleaved caspase-3. Furthermore, osteoblasts were overexpressed with Septin4 and the mechanism via which melatonin induces osteoblast erS was demonstrated to be via the regulation of Septin4. in addition, it was indicated that cytoskeleton destruction, cell morphology changes and the decrease in the number of cells were aggravated after osteoblasts were overexpressed with Septin4, as indicated by phalloidin and daPi staining. collectively, the present results suggest that the Septin4 protein may be a target of erS in melatonin-induced osteoblast apoptosis, which is involved in bone metabolism diseases, thus providing novel evidence for clinical melatonin treatment of iS.

Deacetylation of Septin4 by SIRT2 (Silent Mating Type Information Regulation 2 Homolog-2) Mitigates Damaging of Hypertensive Nephropathy

“…Septin4 accumulates in the brain dopaminergic cells and can cause cell death and the development of Parkinson disease. 11 Meanwhile, inhibiting the expression of septin4 may alleviate liver fibrosis in Schistosoma japonicum infection, 41 reduce osteoblast cytoskeleton destruction, 42 decrease hypoxia-induced cardiomyocyte apoptosis, 12 and alleviate A/R-induced cardiomyopathy. 13 The role of septin4 in hypertensive renal damage has not been previously reported.…”

Integrated spatial transcriptome and metabolism study reveals metabolic heterogeneity in human injured brain

“…It can also regulate the endoplasmic reticulum stress in osteoblasts and further induce apoptosis. 19 Overexpressed septin4 could trigger cytoskeleton destruction, cell morphology changes, and cell loss. These findings are consistent with our study that higher SEPTIN4 in injured brain is mapped to neuronal loss area.…”

High doses of dexamethasone induce endoplasmic reticulum stress-mediated apoptosis by promoting calcium ion influx-dependent CHOP expression in osteoblasts

“…However, under excessive ER stress, the synthesis of ATF4 and ATF3 increases, promoting the expression of CHOP. High levels of CHOP activate the apoptotic pathway and accelerate the apoptosis of osteoblasts, leading to osteoporosis [15,16]. Although both Dex and ER stress induce osteoporosis by mediating osteoblast apoptosis, whether Dex leads to osteoblast apoptosis by inducing osteoblast ER stress is not clear.…”