Effect of H₂S on the circadian rhythm of mouse hepatocytes.
BACKGROUND
Dysregulation 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.


RESULTS
We 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.


CONCLUSIONS
Exogenous 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.
Department of Physiology and Pathophysiology, Fudan University Shanghai Medical College, Shanghai 200032, PR China.
Zhanxian
Z
Shang
Chao
C
Lu
Sifeng
S
Chen
Luchun
L
Hua
Ruizhe
R
Qian
D056930:ARNTL Transcription Factors / Q000235:genetics / Q000378:metabolism; D000818:Animals; D056926:CLOCK Proteins / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D002940:Circadian Rhythm / Q000187:drug effects* / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D006862:Hydrogen Sulfide / Q000494:pharmacology*; D050356:Lipid Metabolism / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D056953:Nuclear Receptor Subfamily 1, Group D, Member 1 / Q000235:genetics / Q000378:metabolism; D056950:Period Circadian Proteins / Q000235:genetics / Q000378:metabolism; D061251:Primary Cell Culture; D019163:Reducing Agents / Q000494:pharmacology*; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism
D056930:ARNTL Transcription Factors; C538961:Bmal1 protein, mouse; C498262:Nr1d1 protein, mouse; D056953:Nuclear Receptor Subfamily 1, Group D, Member 1; C513312:Per2 protein, mouse; D056950:Period Circadian Proteins; D019163:Reducing Agents; D056926:CLOCK Proteins; C538944:Clock protein, mouse; C470545:Sirt1 protein, mouse; D056564:Sirtuin 1; D006862:Hydrogen Sulfide