抵抗素是一种脂肪细胞分泌的多肽类激素,是富含半胱氨酸的分泌性蛋白质,属于抵抗素样分子（resistin-like molecules,RELMs）,又称FIZZs（found in inflammatory zone）家族成员。啮齿类动物抵抗素主要由脂肪细胞特异性分泌：而人抵抗...抵抗素是一种脂肪细胞分泌的多肽类激素,是富含半胱氨酸的分泌性蛋白质,属于抵抗素样分子（resistin-like molecules,RELMs）,又称FIZZs（found in inflammatory zone）家族成员。啮齿类动物抵抗素主要由脂肪细胞特异性分泌：而人抵抗素则主要在外周血单核细胞中表达，并在向巨噬细胞分化时表达增加，展开更多
The canalicular membrane represents the excretory pole of hepatocytes.Bile is an important route of elimination of potentially toxic endo-and xenobiotics(including drugs and toxins),mediated by the major canalicular t...The canalicular membrane represents the excretory pole of hepatocytes.Bile is an important route of elimination of potentially toxic endo-and xenobiotics(including drugs and toxins),mediated by the major canalicular transporters:multidrug resistance protein 1(MDR1, ABCB1),also known as P-glycoprotein,multidrug resistance-associated protein 2(MRP2,ABCC2),and the breast cancer resistance protein(BCRP,ABCG2).Their activities depend on regulation of expression and proper localization at the canalicular membrane,as regulated by transcriptional and post-transcriptional events,respectively.At transcriptional level,specific nuclear receptors(NR)s modulated by ligands,co-activators and co-repressors,mediate the physiological requirements of these transporters.This complex system is also responsible for alterations occurring in specific liver pathologies.We briefly describe the major ClassⅡNRs, pregnane X receptor(PXR)and constitutive androstane receptor(CAR),and their role in regulating expression of multidrug resistance proteins.Several therapeutic agents regulate the expression of relevant drug transporters through activation/inactivation of these NRs.We provide some representative examples of the action of therapeutic agents modulating liver drug transporters, which in addition,involve CAR or PXR as mediators.展开更多
文摘抵抗素是一种脂肪细胞分泌的多肽类激素,是富含半胱氨酸的分泌性蛋白质,属于抵抗素样分子（resistin-like molecules,RELMs）,又称FIZZs（found in inflammatory zone）家族成员。啮齿类动物抵抗素主要由脂肪细胞特异性分泌：而人抵抗素则主要在外周血单核细胞中表达，并在向巨噬细胞分化时表达增加，
基金Grants from Agencia Nacional de Promoción Científicay Tecnológica (PICT N° 05-26306)Consejo Nacional de Investigaciones Científicasy Técnicas (PIP N° 6442)Universidad Nacional de Rosario,Argentina
文摘The canalicular membrane represents the excretory pole of hepatocytes.Bile is an important route of elimination of potentially toxic endo-and xenobiotics(including drugs and toxins),mediated by the major canalicular transporters:multidrug resistance protein 1(MDR1, ABCB1),also known as P-glycoprotein,multidrug resistance-associated protein 2(MRP2,ABCC2),and the breast cancer resistance protein(BCRP,ABCG2).Their activities depend on regulation of expression and proper localization at the canalicular membrane,as regulated by transcriptional and post-transcriptional events,respectively.At transcriptional level,specific nuclear receptors(NR)s modulated by ligands,co-activators and co-repressors,mediate the physiological requirements of these transporters.This complex system is also responsible for alterations occurring in specific liver pathologies.We briefly describe the major ClassⅡNRs, pregnane X receptor(PXR)and constitutive androstane receptor(CAR),and their role in regulating expression of multidrug resistance proteins.Several therapeutic agents regulate the expression of relevant drug transporters through activation/inactivation of these NRs.We provide some representative examples of the action of therapeutic agents modulating liver drug transporters, which in addition,involve CAR or PXR as mediators.
