Enhanced expression of basolateral multidrug resistance protein isoforms Mrp3 and Mrp5 in rat liver by LPS
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M. G. Donner
Abstract
Lipopolysaccharide (LPS) induces hepatocellular downregulation and endocytic retrieval of multidrug resistance protein 2 (Mrp2, Abcc2). Basolateral Mrp isoforms may compensate for the intracellular metabolic changes in cholestasis. Therefore, the effect of LPS on the zonal localization of Mrp2 and Mrp3 and the expression of Mrp3, Mrp4, Mrp5, and Mrp6 mRNA were investigated in rat liver. In normal rat liver Mrp3 was found in pericentral hepatocytes also expressing glutamine synthetase. In LPS-treated rat liver the decrease in Mrp2 protein was most pronounced in pericentral hepatocytes, with only minor down-regulation in periportal hepatocytes. Conversely, induction of Mrp3 was found in pericentral hepatocytes with a low expression of Mrp2. Furthermore, we found a strong induction of Mrp5 mRNA. Likewise, Mrp6 mRNA was upregulated, however Mrp6 protein expression was not significantly altered. It is concluded that Mrp3 is inversely regulated to Mrp2 in a zonal pattern and may compensate for the LPSinduced loss of Mrp2 in the perivenous area. Induction of pericentral Mrp3 and upregulation of Mrp5 mRNA may play an important role in the hepatocellular clearance of cholephilic substances and cyclic nucleotides accumulating after LPS treatment.
Copyright © 2004 by Walter de Gruyter GmbH & Co. KG
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Articles in the same Issue
- Oxygen and the Cell
- O2 sensing in the human ductus arteriosus: redox-sensitive K+ channels are regulated by mitochondria-derived hydrogen peroxide
- Oxidative stress in the systemic and cellular responses to intermittent hypoxia
- HIF hydroxylation and cellular oxygen sensing
- Visualization of the three-dimensional organization of hypoxia-inducible factor-1α and interacting cofactors in subnuclear structures
- Modulation of glucokinase expression by hypoxia-inducible factor 1 and upstream stimulatory factor 2 in primary rat hepatocytes
- Redox-sensitive regulation of the HIF pathway under non-hypoxic conditions in pulmonary artery smooth muscle cells
- Measurement of exhaled hydrogen peroxide from rabbit lungs
- Effects of reducing agents on glutathione metabolism and the function of carotid body chemoreceptor cells
- Expression of functional purinergic receptors in pulmonary neuroepithelial bodies and their role in hypoxia chemotransmission
- Remodelling of Ca2+ homeostasis in type I cortical astrocytes by hypoxia: evidence for association with Alzheimer's disease
- Simultaneous exposure of rats to dioxin and carbon monoxide reduces the xenobiotic but not the hypoxic response
- Structure and expression of two kininogen genes in mice
- The central domain of the matrix protein of HIV-1: influence on protein structure and virus infectivity
- Skin secretion of the toad Bombina variegata contains multiple insulin-releasing peptides including bombesin and entirely novel insulinotropic structures
- Inhibition of lentil copper/TPQ amine oxidase by the mechanism-based inhibitor derived from tyramine
- Enhanced expression of basolateral multidrug resistance protein isoforms Mrp3 and Mrp5 in rat liver by LPS
- Critical O2 and NO concentrations in NO-induced cell death in a rat liver sinusoidal endothelial cell line
