This site was found to have two imperfect copies of the motif linked on the consensus steroid hormone receptor half web page TGACCT organized with a spacing of nucleotide . Preceding studies have shown that this J component kinds two DNA protein complexes in hepatocyte nuclear extracts, termed AIIJl and AIIJ, the final of which has some similarities with NF BA . On top of that, quite a few orphan nuclear receptors, this kind of as HNF , EAR, EAR, and ARP , have been proven to interact with this particular J web-site . In truth, HNF induces, whereas EAR , EAR , and ARP l reduce apo A II gene transcription upon binding to this element . In see in the binding of many different nuclear hormone receptors to this J element, it had been no surprise that PPAR could also interact with this particular component.
Certainly, blog directed mutagenesis experiments demonstrated that this DR I motif mediates the results of PPAR and fibrates on apo A II gene expression, whereas EMSA experiments indicated that PPAR RXR heterodimers bind towards the All peptide synthesis services PPRE. Moreover, cross competition experiments indicated that the All PPREt binds PPAR having a equivalent affinity since the classical ACO PPRE. These information hence implicate unequivocally PPAR within the response on the apo A II gene to fibrate hypolipidemic medicines. In see of the proposed part of PPARs in mediating the effects of nutrition on gene expression it’s tempting to speculate that dietary results on apo A II gene expression also may possibly be mediated via transcription factors belonging to the PPAR relatives. The induction of apo A II promoter activity by selected fatty acid derivatives is definitely an argument in help of this hypothesis.
Far more thorough experiments to examine the results of many different nutritional compounds on apo A II expression are now undertaken hop over to this site in our laboratory. In contrast towards the expand in apo A TI mRNA ranges in human hepatocytes and hepatoma cells, hepatic apo A II mRNA levels decrease just after in vivo administration of fibrates to rodents . Nonetheless, in rat liver the decrease in apo A TI mRNA amounts was not associated with altered transcription action of the apo A II gene, whereas in human liver increased apo A H mRNA amounts are linked to PPAR mediated induction of apo A II gene transcription. The various mechanisms involved in this species precise opposite regulation of apo A II mRNA amounts are unclear at present, but quite a few possible hypothesis is usually forwarded.
To begin with, differences may exist between species in both the cis acting components, involved in these regulatory processes, or while in the general promoter construction, resulting in the absence of transcriptional regulation in rats, but not in people. 2nd, qualitative and or quantitative distinctions in trans acting factors current in rodent or human liver may well contribute to species exact responses to sure agents.