Effect of H₂S on the circadian rhythm of mouse hepatocytes.
Effect of H₂S on the circadian rhythm of mouse hepatocytes.
复制标题
H2S对小鼠肝细胞昼夜节律的影响
DOI：
10.1186/1476-511x-11-23
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发表时间：
2012-02-08
影响因子：
4.5
通讯作者：
Qian R
中科院分区：
文献类型：
--
作者：
Shang Z;Lu C;Chen S;Hua L;Qian R
昼夜节律失调可导致脂质代谢疾病。NAD依赖性去乙酰化酶sirtuin-1（SIRT1）是连接脂质代谢与生物钟的重要枢纽，其去乙酰化活性取决于细胞内NAD+/NADH含量的比值。硫化氢（H2S）是一种内源性还原剂，可以影响细胞内氧化还原状态。因此，我们假设外源H2S可以影响sirt1介导的生物钟基因的表达，从而影响机体脂质代谢。也因为肝脏是一个典型的外围生物钟振荡器与脂质代谢密切相关。因此，我们观察了H2S对原代培养肝细胞中4个中心生物钟基因和sirt1基因24小时动态表达的影响。结果用血清休克法建立了具有昼夜节律的肝细胞模型。并检测到生物钟基因的表达水平和峰值逐渐下降，H2S可以在一定时间内维持clock、Per2、Bmal1、rev -erbα等生物钟基因的表达和振幅。因此，H2S组sirt1的表达量明显高于对照组。结论外源还原剂H2S可维持离体肝细胞生物钟基因的昼夜节律。我们推测H2S通过直接或间接改变肝细胞内NAD+/NADH含量比，增强SIRT1蛋白活性，从而维持生物钟基因的表达节律，在预防和治疗生物钟紊乱引起的脂质代谢相关疾病中发挥作用。
BackgroundDysregulation of circadian rhythms can contribute to diseases of lipid metabolism. NAD-dependent deacetylase sirtuin-1(SIRT1) is an important hub which links lipid metabolism with circadian clock by its deacetylation activity depends on intracellular NAD+/NADH content ratio. Hydrogen sulfide (H2S) is an endogenous reductant which can affect the intracellular redox state. Therefore, we hypothesized that exogenous H2S can affect the expression of circadian clock genes mediated by sirt1 thereby affecting body's lipid metabolism. And also because the liver is a typical peripheral circadian clock oscillator that is intimately linked to lipid metabolism. Thus the effect of H2S were observed on 24-hour dynamic expression of 4 central circadian clock genes and sirt1gene in primary cultured hepatocytes.ResultsWe established a hepatocyte model that showed a circadian rhythm by serum shock method. And detected that the expression level and the peak of circadian clock genes decreased gradually and H2S could maintain the expression and amplitude of circadian clock genes such as Clock, Per2, Bmal1 and Rev-erbαwithin a certain period time. Accordingly the expression level of sirt1 in H2S group was significantly higher than that in the control group.ConclusionExogenous reductant H2S maintain the circadian rhythm of clock gene in isolated liver cells. We speculated that H2S has changed NAD+/NADH content ratio in hepatocytes and enhanced the activity of SIRT1 protein directly or indirectly, so as to maintain the rhythm of expression of circadian clock genes, they play a role in the prevention and treatment of lipid metabolism-related disease caused by the biological clock disorders.