Multidrug Resistance Protein 3
Multidrug resistance protein 3 is a protein belonging to the ABC subfamily C [ABCC]3) and it plays a significant role in the protection of hepatocytes as well as other tissues through extreation of different toxic organic conjugates of anion including the bile salts. Expression of multidrug resistance protein 3 or ABCC3 increases in a liver of individuals who are cholestatic but this molecular mechanism of the up-regulation stays elusive.
Basically, multidrug resistance protein 3 is a member of adenosine triphosphate binding cassette, the ABC transporter super-family. It expresses itself in different tissues including kidney, liver, adrenal gland, bladder and intestine of rodents and humans. Multidrug resistance protein 3 is localized in the basolateral membrane of the cells and it excretes sulfated, taurine-conjugated bile salts, glycine and bilirubin glucuronides, leukorienes, 17 x- glucuronosyl, and several drugs.
Hepatic multidrug resistance protein 3 expression under normal physiological circumstances is low. However, this expression is up-regulated significantly as adaptive and protective response when an individual is suffering from cholestasis. The up-regulation is also observed in the liver of a patient during the advance stages of primary biliary cirrhosis. It is also the case for parient with the extrahepatic cholestasis that is caused by pancreatic malignancy. However, it is not the case with patients in their early stages of progressive familial intra-hepatic cholestasis or PBC.
According to these revelations, it has been concluded that the distribution of multidrug resistance protein 3 and the basolateral position that it occupies in polarized cells suggests that the protein play an important role in metabolism when it comes to intestinal uptake of the organic anions as well as removal of the organic acids from liver cells and bile under cholestasic conditions.
The study revealed that multidrug resistance protein 3 up-regulation is high in the liver of the rats that were made cholestatic through litigation of the bile duct. It is also the case in the cholestatic liver of humans. Multidrug resistance protein 3 is also present in adrenal cortex in high levels. This has increased the possibility of multidrug resistance protein 3 being responsible for the secretion of certain hydrophilic steroid home derivatives including the dehydroepiandrosterone sulfate.
Despite being a member of the MRP subfamily that is involved in the development of multi-drug resistance, specific function of multidrug resistance protein 3 is yet to be determined. Nevertheless, it has been proven to play a significant role in the intestinal organic anions excretion and biliary transport.
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