Bile acid sensor

Renga B, Mencarelli A, Cipriani S, et al. The bile acid sensor FXR is required for immune-regulatory activities of TLR-9 in intestinal... 

PXR has been demonstrated to act as an LCA sensor and plays an essential role in detoxification of cholestatic bile acids [11,61]. Studies in different animal models showed that activation of PXR protected against severe liver damage induced by LCA. Pretreatment of wild-type mice, but not the PXR-null mice, with PCN reduced the toxic effects of LCA. Moreover, genetic activation of PXR by expressing the activated... 

Another example in which literature results were reanalyzed in view of the PSSC concept concerns the development of ligands for the farnesoid X receptor. The farnesoid X receptor is a transcriptional sensor for bile acids, the primary products of cholesterol metabolism, and plays an important role in lipid homeostasis. The farnesoid X receptor was, until recently, an orphan receptor, which means that no specific ligands existed for this receptor. Selective ligands for this receptor have been found in natural product libraries described by Nicolaou et al. The group of Nicolaou developed solid phase synthesis methods to make combinatorial libraries based on a benzopyran core structure. " A 10,000-membered combinatorial library based on the benzopyran core structure was synthesized and screened for activity on the farnesoid X receptor. The first specific ligands for the... 

FXR is a well-characterized member of the metabolic subfamily of NRs and is a transcriptional sensor for bile acids [35]. Its ligands, including chenodeoxy-cholic acid (CDCA 37) (Fig. 8-10), act as signaling molecules and participate in an intricate network of interactions that ultimately govern lipid, steroid, and cholesterol homeostasis and are involved in processes such as glucose utilization, inflammation, and carcinogenesis [35]. Maloney et al. reported GW4064... 

In addition to PXR and CAR, several other nuclear receptors, such as vitamin D receptor (VDR), hepatocyte nuclear factor 4a (HNF4a), peroxisome proliferator-activated receptors (PPARs), and farnesoid X receptor (FXR), have also been implicated in the regulation of xenobiotic enzymes and transporters [9-12], More recently, results from our lab have shown that the liver X receptor (LXR), a previously known sterol sensor, can also regulate the expression of phase II SULTs, such as the bile acid detoxifying hydroxysteroid sulfotransferase Sult2a9/2al [13] and the estrogen sulfotransferase (Est/Sultlel) [14],... 

Unlike the steroid receptors, most of which function as homodimers, a second class of NRs function as heterodimers with the retinoid X receptor (RXR). Importantly, these receptors serve as sensors for metabolites such as fatty acids, oxysterols, and bile acids. Key elements of ligand recognition and receptor activation have been elucidated following structure-function analyses of several receptors in this family including the PPARs, liver X receptors (LXRs), and FXR. 

Cholesterol and its fatty acid esters are important components of nerve and brain cells and are precnrsors of the biological materials snch as bile acids and steroid hormones. Accumulation of cholesterol in blood leads to fatal diseases such as arteriosclerosis, cerebral thrombosis and coronary diseases. Kajiya and co-workers immobilised cholesterol oxidase (ChOx) and ferrocene carboxylate in PPy electrochemically to describe the sensitivity of the resulting films [188]. The response was proportional to the cholesterol concentration up to 0.05 mM. It has been demonstrated that ferrocene attached to polymer chains can mediate electron transfer from horseradish peroxidase (HRP) to a conventional electrode surface [189]. In the case of immobilised HRP and ChOx the sensor yields 0.35 i,A to 10 mM of cholesterol whereas 3 pA was obtained in the case of free ChOx. It was therefore suggested that the sensor response is limited by the interfacial transport or reaction rate of H2O2. The sensor response was also found to be independent of the applied potential between -100 and 100 mV. 

Maitra, U. Nath, S. Bile acid derived PET-based cation sensors molecular structure dependence of their sensitivity. Chem. Aslan J. 2009,4, 989-997. 

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