Background Trace elements function as essential cofactors that are involved in various biochemical processes in mammals. Autophagy is vital for nutrient supplement, which is an important Zeitegber for the circadian homeostasis in heart. Here, we considered the possibility that autophagy, as well as the cardiomyocyte clock and glycolysis are interlinked. Detrimental effects were observed when cardiac system is exposed to bromine containing drugs. This study investigated the effects and mechanisms of bromide on the circadian clock and glycolytic metabolism of H9C2 cardiomyocytes.
Methods H9C2 cardiomyocytes were incubated with sodium bromide at indicated doses for 24 hours, cell viability, mRNA expression of clock genes, glycolytic genes and autophagic genes were examined using various cellular and molecular approaches. Also, circadian oscillation rhythm of these genes was determined by serum shock with sodium bromide or equal amounts of sodium chloride.
Results Bromide modestly affects cell viability and apoptosis of H9C2 cardiomyocytes. Bromide dampens the clock and glycolytic ( Hk2 and Pkm2 ) gene expression rhythmicity in a dose-dependent manner. Additionally, bromide inhibits autophagic process in H9C2 cardiomyocytes. In contrast, rapamycin (an autophagy inducer) dramatically restores the inhibitory effect of NaBr on the mRNA expression levels of clock genes ( Bmal1 , Cry1 and Rorα ) and glycolytic genes ( Hk2 and Pkm2 ).
Conclusions Our results reveal that bromide represses the clock and glycolytic gene expression patterns, partially through inhibition of autophagy.