Role of sirtuin 1 in the brain development in congenital hypothyroidism rats via the regulation of p53 signaling pathway

Abstract

The present study aimed to investigate the expression, role, and underlying mechanism of action of sirtuin 1 (SIRT1) in congenital hypothyroidism (CH). A CH model was established in rats, and neuronal cells were isolated from the hippocampal tissues of normal rats. Free thyroxine (fT4) and thyroid-Stimulating hormone (TSH) concentrations were determined to confirm CH model conduction. The cognitive behavior of rats with CH was examined using open field and forced swimming tests. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting were used to detect the expression levels of SIRT1, p53, B-cell lymphoma-extra-large (Bcl-xl), Bcl-2-associated X (Bax), and cytochrome c in the hippocampal tissues and neuronal cells. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay and flow cytometry were performed to evaluate cell viability and apoptosis, respectively. The results revealed that SIRT1 was expressed at low levels in the hippocampal tissues of rats with CH. Moreover, overexpression of SIRT1 in the hippocampal tissues of rats with CH and improved rat behavior, while reducing the CH-induced nerve cell apoptosis. In addition, this overexpression increased the viability, inhibited apoptosis, and reduced the expression of p53, Bax, and cytochrome c, while increasing the expression of Bcl-xl in cultured neurons. In contrast, SIRT1-small interfering RNA exhibited the opposite effects in cultured neurons. In conclusion, SIRT1 plays a role in the occurrence and development of CH by regulating nerve cell apoptosis.

The sirtuin family in health and disease

“…The overexpression of SIRT1 resulted in markedly reduced mRNA and protein expression levels of p53 signaling pathway-related molecules (including p53 and Bax) in vitro, but increased Bcl mRNA and protein expression. 212 p53 expression gradually decreased with increasing SIRT1 levels, thus indicating a gradual decrease in apoptosis. 213 These findings thus show that SIRT1 inhibits apoptosis via inactivation of p53, suggesting a critical role for SIRT1 in regulating the p53 signaling pathway.…”

Editorial: Hydrogen sulfide: Physiology, Pharmacology and Toxicology, Volume II

“…Hypothyroidism is characterized by the disruption of thyroid hormone synthesis and secretion by thyrocytes ( Zhang et al, 2021 ). Sirtuin-1 (SIRT1) inactivation is involved in thyroid cell damage and thyroid hormone deficiency ( Wei et al, 2022 ). H 2 S, as a gas signaling molecule, participates in many physiopathologic processes by upregulating SIRT1 ( Yang et al, 2021 ).…”