These variations in the CYP24A1 response not only confirm the high sensitivity of this particular cell line to xenobiotic exposure but also provide further evidence to support the role of VDR as a potential target for xenobiotics that is able to bind structurally diverse endogenous and exogenous compounds and modulate activity of other important genes accordingly.
Diseases that fall into the category of metabolic liver diseases are generally considered to include disorders of hepatic synthesis and degradation or regulation of a diverse variety of endogenous compounds.
PXR is a ligand-dependent transcription factor with agonists and antagonists encompassing wide range of structurally diverse endogenous and exogenous compounds.
Our results replicate these findings and also show that genes harbouring age-demethylated CpGs are enriched in genes related to the response to diverse stimuli including endogenous compounds and organic and chemical substances.
PXR agonists include a wide range of structurally diverse endogenous and exogenous compounds such as bile acids, steroid hormones, dietary fat-soluble vitamins, prescription medications, and herbal drugs, as well as environmental chemicals such as pesticides, estrogens, and antiestrogens (Mnif et al. 2007).
MRP4 can pump out diverse endogenous and xenobiotic organic anionic compounds along with their phase II metabloites, thereby conferring resistance to various cytotoxic compounds and, in turn, protecting crucial tissues against them [11], [93].
Cloning and functional studies of GPCRs have revealed that the superfamily of GPCRs comprises receptors for chemically diverse native ligands including (1) endogenous compounds like amines, peptides, and Wnt proteins (i.e., secreted proteins activating Frizzled receptors); (2) endogenous cell surface adhesion molecules; and (3) photons and exogenous compounds like odorants.
It is activated by a structurally diverse array of xenobiotics and endogenous compounds, including bile acids and steroid hormones [ 13, 17, 18].
It metabolizes many endogenous compounds and is relevant in carcinogenesis due to its ability to modify diverse promutagen and procarcinogen xenobiotics [3].
While UGTs metabolize various clinically used drugs, they are also involved in metabolism of endogenous compounds, such as bilirubin – a specific substrate of UGT1A16.
