Induction of Multidrug Resistance-Associated Protein MRP3 in the Liver of Rats Fed with Docosahexaenoic Acid

Kubo, Kazuhiro; Sekine, Seiji; Saito, Morio

doi:10.1271/bbb.60019

Cited by 9 publications

(8 citation statements)

References 37 publications

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“…These include Sp1, Sp3, PXR, CAR, Ahr, PPARα, Nrf2, and RXRa:RXRa. 6-8,22-27 Kubo et al 28 have shown that docosahexanoic acid induces Mrp3, further supporting our observation that Mrp3 is induced with lipid mixtures as well as FBS. The mechanisms for the effects we report here may well involve the interaction of multiple signaling modes and remain to be determined.…”

Section: Discussionsupporting

confidence: 85%

Multidrug Resistance-Associated Protein 3 (Mrp3/Abcc3/Moat-D) Is Expressed in the SAE Squalus acanthias Shark Embryo–Derived Cell Line

Kobayashi

Parton²,

Czechanski³

et al. 2007

Zebrafish

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The multidrug resistance-associated protein 3 (MRP3/Mrp3) is a member of the ATP-binding cassette (ABC) protein family of membrane transporters and related proteins that act on a variety of xenobiotic and anionic molecules to transfer these substrates in an ATP-dependent manner. In recent years, useful comparative information regarding evolutionarily conserved structure and transport functions of these proteins has accrued through the use of primitive marine animals such as cartilaginous fish. Until recently, one missing tool in comparative studies with cartilaginous fish was cell culture. We have derived from the embryo of Squalus acanthias, the spiny dogfish shark, the S. acanthias embryo (SAE) mesenchymal stem cell line. This is the first continuously proliferating cell line from a cartilaginous fish. We identified expression of Mrp3 in this cell line, cloned the molecule, and examined molecular and cellular physiological aspects of the protein. Shark Mrp3 is characterized by three membrane-spanning domains and two nucleotide-binding domains. Multiple alignments with other species showed that the shark Mrp3 amino acid sequence was well conserved. The shark sequence was overall 64% identical to human MRP3, 72% identical to chicken Mrp3, and 71% identical to frog and stickleback Mrp3. Highest identity between shark and human amino acid sequence (82%) was seen in the carboxyl-terminal nucleotide-binding domain of the proteins. Cell culture experiments showed that mRNA for the protein was induced as much as 25-fold by peptide growth factors, fetal bovine serum, and lipid nutritional components, with the largest effect mediated by a combination of lipids including unsaturated and saturated fatty acids, cholesterol, and vitamin E.

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Section: Discussionsupporting

confidence: 85%

Multidrug Resistance-Associated Protein 3 (Mrp3/Abcc3/Moat-D) Is Expressed in the SAE Squalus acanthias Shark Embryo–Derived Cell Line

Kobayashi

Parton²,

Czechanski³

et al. 2007

Zebrafish

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“…AMP-regulated kinase (AMPK) is a central regulator of lipid metabolism in the liver [74][75][76]. Its phosphorylation and thereby activation by the upstream kinase complex LKB1/STRAD-MO25 leads to inhibition of fatty acid synthesis, lipogenesis and triglyceride synthesis while stimulating anti-lipogenic metabolic pathways like fatty acid oxidation and ketogenesis [77][78][79]. Dephosphorylation and inactivation of AMPK on the contrary stimulates fatty acid synthesis, lipogenesis and triglyceride synthesis, which in turn causes steatosis in the chronic setting.…”

Section: Discussionmentioning

confidence: 99%

Pathological implications of cadherin zonation in mouse liver

Hempel

Schmitz

Winkler

et al. 2015

Cell. Mol. Life Sci.

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Both acute and chronic liver diseases are associated with ample re-modeling of the liver parenchyma leading to functional impairment, which is thus obviously the cause or the consequence of the disruption of the epithelial integrity. It was, therefore, the aim of this study to investigate the distribution of the adherens junction components E- and N-cadherin, which are important determinants of tissue cohesion. E-cadherin was expressed in periportal but not in perivenous hepatocytes. In contrast, N-cadherin was more enriched towards the perivenous hepatocytes. In agreement, β-catenin, which links both cadherins via α-catenin to the actin cytoskeleton, was expressed ubiquitously. This zonal expression of cadherins was preserved in acute liver injury after treatment with acetaminophen or partial hepatectomy, but disrupted in chronic liver damage like in non-alcoholic steatohepatitis (NASH) or α1-antitrypsin deficiency. Hepatocyte proliferation during acetaminophen-induced liver damage was predominant at the boundary between the damaged perivenous and the intact periportal parenchyma indicating a minor contribution of periportal hepatocytes to liver regeneration. In NASH livers, an oval cell reaction was observed pointing to massive tissue damage coinciding with the gross impairment of hepatocyte proliferation. In the liver parenchyma, metabolic functions are distributed heterogeneously. For example, the expression of phosphoenolpyruvate carboxykinase and E-cadherin overlapped in periportal hepatocytes. Thus, during liver regeneration after acute damage, the intact periportal parenchyma might sustain essential metabolic support like glucose supply or ammonia detoxification. However, disruption of epithelial integrity during chronic challenges may increase susceptibility to metabolic liver diseases such as NASH or vice versa. This might suggest the regulatory integration of tissue cohesion and metabolic functions in the liver.

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“…Fasting causes a metabolism shift from lipid storage to lipid oxidation for energy generation, resulting in fat mobilization from adipose to liver, and consequently increasing lipid peroxidation products (1). Lipid breakdown in fasting preferentially increases arachidonic acid, stearic acid and docosahexanoic acid, which are probable substrates for Abcc3 (12,29). A consequence of fasting is hepatic lipid accumulation and break down, as well as, increased bilirubin, bile acids, and cyclic nucleotides, which are all substrates for Abcc2-4.…”

Section: Discussionmentioning

confidence: 99%

Fasting Induces Nuclear Factor E2-Related Factor 2 and ATP-Binding Cassette Transporters via Protein Kinase A and Sirtuin-1 in Mouse and Human

Kulkarni

Donepudi

et al. 2014

Antioxidants & Redox Signaling

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Aims: The purpose of this study was to determine whether 3¢-5¢-cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA) and Sirtuin-1 (SIRT1) dependent mechanisms modulate ATP-binding Cassette (ABC) transport protein expression. ABC transport proteins (ABCC2-4) are essential for chemical elimination from hepatocytes and biliary excretion. Nuclear factor-E2 related-factor 2 (NRF2) is a transcription factor that mediates ABCC induction in response to chemical inducers and liver injury. However, a role for NRF2 in the regulation of transporter expression in nonchemical models of liver perturbation is largely undescribed. Results: Here we show that fasting increased NRF2 target gene expression through NRF2-and SIRT1-dependent mechanisms. In intact mouse liver, fasting induces NRF2 target gene expression by at least 1.5 to 5-fold. In mouse and human hepatocytes, treatment with 8-Bromoadenosine-cAMP, a cAMP analogue, increased NRF2 target gene expression and antioxidant response element activity, which was decreased by the PKA inhibitor, H-89. Moreover, fasting induced NRF2 target gene expression was decreased in liver and hepatocytes of SIRT1 liver-specific null mice and NRF2-null mice. Lastly, NRF2 and SIRT1 were recruited to MAREs and Antioxidant Response Elements (AREs) in the human ABCC2 promoter. Innovation: Oxidative stress mediated NRF2 activation is well described, yet the influence of basic metabolic processes on NRF2 activation is just emerging. Conclusion: The current data point toward a novel role of nutrient status in regulation of NRF2 activity and the antioxidant response, and indicates that cAMP/PKA and SIRT1 are upstream regulators for fasting-induced activation of the NRF2-ARE pathway. Antioxid. Redox Signal. 20,[15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30]

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Induction of Multidrug Resistance-Associated Protein MRP3 in the Liver of Rats Fed with Docosahexaenoic Acid

Cited by 9 publications

References 37 publications

Multidrug Resistance-Associated Protein 3 (Mrp3/Abcc3/Moat-D) Is Expressed in the SAE Squalus acanthias Shark Embryo–Derived Cell Line

Multidrug Resistance-Associated Protein 3 (Mrp3/Abcc3/Moat-D) Is Expressed in the SAE Squalus acanthias Shark Embryo–Derived Cell Line

Pathological implications of cadherin zonation in mouse liver

Fasting Induces Nuclear Factor E2-Related Factor 2 and ATP-Binding Cassette Transporters via Protein Kinase A and Sirtuin-1 in Mouse and Human

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