Dexamethasone- and osmolarity-dependent expression of the multidrug-resistance protein 2 in cultured rat hepatocytes1

Kubitz, Ralf; Warskulat, Ulrich; Schmitt, Marcus; Häussinger, Dieter

doi:10.1042/bj3400585

Cited by 44 publications

(10 citation statements)

References 30 publications

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“…Hypoosmolarity increases, whereas hyperosmolarity decreases mRNA and protein levels of MRP2 in isolated rat hepatocytes. 73 Thus, as it is observed for Bsep, 68 also Mrp2 regulation by cell hydration occurs at the level of both short-term regulation and gene expression.…”

Section: Osmoregulation Of Mrp2mentioning

confidence: 78%

Short-Term Regulation of Canalicular Transport

Häussinger¹,

Schmitt²,

Weiergräber³

et al. 2000

Semin Liver Dis

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On a short term basis, canalicular secretion is under control of the hepatocellular hydration state, substrates, cytokines, toxins, and hormones. Regulation occurs at the level of substrate availability, covalent modification of transporters, and their regulated exocytic insertion into or endocytic retrieval from the membrane. A variety of signal transduction pathways involving the activation of mitogen-activated protein kinases, protein kinases A and C, participates in these processes. However, much has still to be learned about the crosstalk of different signaling systems and their molecular targets that determine the outcome for canalicular secretion.

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Section: Osmoregulation Of Mrp2mentioning

confidence: 78%

Short-Term Regulation of Canalicular Transport

Häussinger¹,

Schmitt²,

Weiergräber³

et al. 2000

Semin Liver Dis

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“…Oxidation and conjugation change weakly cationic drugs into anionic compounds and increase their water solubility. Negatively charged toxins can now leave the microvillar compartment via large anion channels of the MOAT type that have been identified as MRP2 residing in apical microvilli of hepatocytes (Kubitz et al, 1999; Kikuchi et al, 2002).…”

Section: ‘Multidrug Resistance’—a Natural Plasma Membrane Cleaning Mementioning

confidence: 99%

Fundamental role of microvilli in the main functions of differentiated cells: Outline of an universal regulating and signaling system at the cell periphery

Lange¹

2011

Journal Cellular Physiology

107

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Until now, the general importance of microvilli present on the surface of almost all differentiated cells has been strongly underestimated and essential functions of these abundant surface organelles remained unrecognized. Commonly, the role of microvilli has been reduced to their putative function of cell-surface enlargement. In spite of a large body of detailed knowledge about the specific functions of microvilli in sensory receptor cells for sound, light, and odor perception, their functional importance for regulation of basic cell functions remained obscure. Here, a number of microvillar mechanisms involved in fundamental cell functions are discussed. Two structural features enable the extensive functional competence of microvilli: First, the exclusive location of almost all functional important membrane proteins on microvilli of differentiated cells and second, the function of the F-actin-based cytoskeletal core of microvilli as a structural diffusion barrier modulating the flow of low molecular substrates and ions into and out of the cell. The specific localization on microvilli of important functional membrane proteins such as glucose transporters, ion channels, ion pumps, and ion exchangers indicate the importance and diversity of microvillar functions. In this review, the microvillar mechanisms of audioreceptor, photoreceptor, and olfactory/taste receptor cells are discussed as highly specialized adaptations of a general type of microvillar mechanisms involved in regulation of important basic cell functions such as glucose transport/energy metabolism, ion channel regulation, generation and modulation of the membrane potential, volume regulation, and Ca signaling. Even the constitutive cellular defence against cytotoxic compounds, also called "multidrug resistance (MDR)," is discussed as a microvillar mechanism. A comprehensive examination of the specific properties of "cable-like" ion conduction along the microvillar core structure of F-actin allows the proposal that microvilli are specifically designed for using ionic currents as cellular signals. In view of the multifaceted gating and signaling properties of TRP channels, the possible role of microvilli as a universal gating device for TRP channel regulation is discussed. Combined with the role of the microvillar core bundle of actin filaments as high-affinity Ca store, microvilli may turn out as highly specialized Ca signaling organelle involved in store-operated Ca entry (SOCE) and initiation of nonlinear Ca signals such as waves and oscillations.

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“…Tauro-UDCA was shown to induce rapid vesicular insertion of the bile salt export pump Bsep and the bilirubin transporter Mrp2 via the p38 MAPK [76,77] and protein kinase C [78,79]. These canalicular transporters are not only regulated by lipopolysaccharide [80], dexamethasone [80], and drugs [81], but also by the cellular hydration state [80,82,83]. Hypoosmotic liver cell swelling increases within minutes the transport capacity for bile salts [84] in an α 5 β 1 -integrin-, c-Src-kinase-, MAP-kinase-and microtubule-dependent manner [85,86].…”

Section: Treatment Of Mdr3-related Liver Diseasesmentioning

confidence: 99%

Cholestatic Liver Diseases from Child to Adult: The Diversity of MDR3 Disease

et al. 2011

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The phospholipidfloppase MDR3 (gene symbol: ABCB4) is expressed in the canalicular membrane of hepatocytes and mediates the biliary excretion of phosphatidylcholine, which is required for the formation of mixed micelles in bile. Several mutations of ABCB4 have been identified, which cause cholestatic liver diseases of varying severity including progressive familial intrahepatic cholestasis type 3 (PFIC-3), intrahepatic cholestasis of pregnancy (ICP) and the low phospholipid associated cholelithiasis syndrome (LPAC). Here, we report on four new (S1076N; L 23Hfs16X; c.286 + 1G > A; Q 1181E) and one known (S27G) MDR3 mutations in eight patients of three families. The patients presented with a wide spectrum of liver diseases. The clinical presentation and decisive laboratory findings or the association to a trend-setting family history led to the identification of the genetic background in these patients. Even the same mutation may be associated with varying disease progression.

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Dexamethasone- and osmolarity-dependent expression of the multidrug-resistance protein 2 in cultured rat hepatocytes1

Cited by 44 publications

References 30 publications

Short-Term Regulation of Canalicular Transport

Short-Term Regulation of Canalicular Transport

Fundamental role of microvilli in the main functions of differentiated cells: Outline of an universal regulating and signaling system at the cell periphery

Cholestatic Liver Diseases from Child to Adult: The Diversity of MDR3 Disease

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