SIRT1, Cellular Stress and Metabolism

Sirtuin 1 (SIRT1), also known as NAD-dependent deacetylase sirtuin-1, is an enzyme with deacetylase activity, and has been shown to target regulatory factors involved in cellular stress and metabolism.  It has been reported that SIRT1 is inhibited by heme-induced oxidative stress. In a recent study, a group of researchers speculated that because butyric acid (BA) induces blood mitochondrial oxidative stress (when retained in tissue), it can also inhibit SIRT1.

Rats were injected with BA to cause BA retention in the gingival tissue, and the induction of cytosolic oxidative stress was then assessed in blood samples.  It was shown that BA retention did cause oxidative stress, which was correlated to an observed increase in heme, catalase and H2O2.  It was also speculated that BA retention was causing mitochondrial oxidative stress.  If the mitochondrion was also experiencing an increase in heme and reactive oxygen species (ROS), like H2O2, this would further cause the activation of NADPH oxidase (NOX) in the mitochondria.  This postulation was confirmed by observing an increase in the amount of NOX and NADP+ in the blood.  The observed increase in NADP+ caused these researchers to investigate the amount of NAD+ kinase (NADK) in the blood, and found an increase in this enzyme. Therefore, the expected decrease in the amount of NAD+ was also observed.  Lastly, the investigators were led to determine how SIRT1 would be affected by the cellular stress caused by BA.  As expected, there was an observed decrease in the amount of SIRT1, which is dependent on NAD+.  Because SIRT1 is important in promoting cell survival and regulating the cellular stress response, a decrease in this enzyme could be detrimental for the cell.


The original research paper was published in:

Butyric acid-induced rat jugular blood cytosolic oxidative stress is associated with SIRT1 decrease.

This experiment made use of one of StressMarq Biosciences’ Hsp60 antibodies to verify the purity of the cytosolic samples by determining level of heat-shock protein 60 in the blood cytosol extracts.

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