Mechanisms of regulation of liver fatty acid-binding protein

Kaikaus, R.M.; Chan, William K.; Montellano, Paul R. Ortiz de; Bass, Nathan M.

doi:10.1007/978-1-4615-3096-1_12

Cited by 9 publications

(13 citation statements)

References 48 publications

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“…PPARresponsive elements have been identified in several gene promoters, including those of each of the three enzymes of the peroxisomal (3-oxidation cycle (11)(12)(13), the cytochrome P450 4A6 enzyme (14), and the rat liver FA binding protein (29). Cytochrome P450 4A1 has also been implicated as a target for this factor (26). The products of each of these genes are involved in extramitochondrial FA catabolism, but the present work describes a PPAR gene target for a mitochondrial enzyme.…”

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confidence: 90%

“…Although previous reports have indicated that exogenously administered dodecanedioic acid is inactive in stimulating PPAR-mediated transactivation (24,25), the induction of the PPAR with CPT-I inhibition indicates that P450 metabolites should not be excluded as candidate PPAR ligands. Support for this hypothesis includes the observation that the gene encoding P450 4A1, the rate-limiting enzyme in w>oxidation, is upregulated during CPT-I inhibition, and direct inhibition of 4A1 impairs PPAR activator-dependent induction of responsive gene mRNA accumulation (26). Alternatively, neutral acyl steroid esters formed from accumulated thioesters are candidate PPAR ligands.…”

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The peroxisome proliferator-activated receptor regulates mitochondrial fatty acid oxidative enzyme gene expression.

Gulick

Cresci

Caira

et al. 1994

Proc. Natl. Acad. Sci. U.S.A.

498

328

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Medium-chain acyl-CoA dehydrogenase (MCAD) catalyzes a pivotal reaction in mitochondrial fatty acid (FA) «-oxidation. To examine the potential role of FAs and their metabolites in the regulation of MCAD gene expression, we measured MCAD mRNA levels in animals fed inhibitors of mitochondrial long-chain FA import. Admintation of carnitine palmitoyltransferase I inhibitors to mice or rats resulted in tissue-limited increases in steady-state MCAD mRNA levels. HepG2 cell cotransfection experiments with MCAD promoter reporter plasmids demonstrated that this was a transcriptional effect mediated by the peroxisome proliferator-activated receptor (PPAR). The activity mapped to a nuclear receptor response element that functioned in a heterologous promoter context and specifically bound immunoreactive PPAR in rat hepatic nuclear extracts, confirming an in vivo interaction. PPAR-mediated transactivations of this promoter and element were also induced by exogenously added FA and fibric acid derivatives. Induction of PPAR transactivation by perturbation of this discrete metabolic step is unusual and indicates that intracellular FA metabolites that accumulate during such inhibition can regulate MCAD expression and are likely candidates for PPAR ligand(s). These results dictate an expanded role for the PPAR in the regulation of FA metabolism.The flavoenzyme medium-chain acyl-CoA dehydrogenase [MCAD; acyl-CoA:(acceptor) 2,3-oxidoreductase; EC 1.3.99.3] is one of four different chain-length-specific enzymes that catalyze the initial reaction in the mitochondrial fatty acid (FA) (3-oxidation cycle (1, 2). Substrates for MCAD include medium-chain length (C6-C12) acyl-CoA thioesters derived from (i) medium-chain FAs that enter mitochondria by diffusion, (ii) products of mitochondrial (-oxidation of saturated and unsaturated long-chain FAs, and (iii) products ofperoxisomal (-oxidation oflong-chain and very long-chain FAs. Because these diverse pathways of FA oxidation converge at this point, MCAD catalyzes a pivotal step in cellular FA metabolism.Expression of MCAD is highly regulated by a variety of conditions that alter substrate availability and tissue energy demands. MCAD mRNA and enzyme are expressed predominantly in tissues that use FAs preferentially as energy substrates, including heart, liver, slow-twitch skeletal muscle, and kidney (3). Hepatic and cardiac MCAD mRNA are markedly upregulated in concert with mitochondrial FA oxidation rates during the postnatal period (3). Induction of MCAD expression is also seen in these tissues during periods of fasting, when cellular energy requirements are met primarily by FA oxidation, an effect that has been attributed to transcriptional modulation (4).The mechanisms-involved in regulation of cellular FA oxidation at the transcriptional level are largely unknown.We have explored the regulation of MCAD promoter activity and have identified sequences that confer both basal (5) and nuclear hormone receptor-mediated activities (6-8). As a further step in delineating the mechanisms ...

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confidence: 90%

mentioning

confidence: 99%

The peroxisome proliferator-activated receptor regulates mitochondrial fatty acid oxidative enzyme gene expression.

Gulick

Cresci

Caira

et al. 1994

Proc. Natl. Acad. Sci. U.S.A.

498

328

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“…A significant decrease in the expression of the L-FABP gene was observed in the livers of HNF1α-null mice. Since PPARα gene expression was unaffected by HNF1α gene inactivation, the difference in the expression of L-FABP gene, a target gene for PPARα (26)(27)(28), between HNF1α-null mice and heterozygous controls is not likely to be related to altered PPARα expression. Other factors that affect L-FABP gene expression include steroids (29).…”

Section: Pretreatment Of Etoxomir-treated Pparα-null Males With Estramentioning

confidence: 99%

Regulation of the Liver Fatty Acid Binding Protein Gene (L-FABP) by Hepatocyte NuclearFactor 1aplha: alterations in fatty acid homeostasis in HNF1alpha-deficient mice

Akiyama

Ward

Gonzalez

2000

Journal of Biological Chemistry

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“…Fibrates have been shown to reduce cisplatin induced AKI [97, 102]. Liver fatty acid binding protein (L-FABP) belongs to a super family of lipid-binding proteins with low molecular weight (14-15 kDa) whose transcription rate is regulated by fibrates through a PPRE located in its promoter region [103, 104]. Most recently, fibrates have been shown to increase L-FAPB and decrease cisplatin-induced AKI [105].…”

Section: Drugs That Block Inflammation and Reduce Cytotoxicity In Acumentioning

confidence: 99%

Immune Mechanisms and Novel Pharmacological Therapies of Acute Kidney Injury

Bajwa

Kinsey²,

Okusa

2009

CDT

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Ischemia-reperfusion injury (IRI) is a major cause of acute kidney injury (AKI) and both innate and adaptive immunity contribute to the pathogenesis. Kidney resident cells promote inflammation after IRI by increasing endothelial cell adhesion molecule expression and vascular permeability. Kidney epithelial cells bind complement and express tolllike receptors and resident and infiltrating cells produce cytokines/chemokines. Early activation of kidney dendritic cells (DCs) initiates a cascade of events leading to accumulation of interferon-γ-producing neutrophils, infiltrating macrophages, CD4+ T cells, B cells and invariant natural killer T (NKT) cells. Recent studies from our laboratory now implicate the IL23/IL17 pathway in kidney IRI. Following the initial early phase of inflammation, the late phase involves infiltration of anti-inflammatory cells including regulatory T cells, alternatively activated macrophages and stem cells leading to attenuation of inflammation and initiation of repair. Based upon these immune mechanisms of injury, recent studies hold promise for novel drug therapies. These pharmacological agents have been shown to reduce inflammation or cytotoxicity in rodent models of AKI and some show early promise in clinical trials. This review summarizes recent advances to further our understanding of the immune mechanisms of AKI and potential pharmacological therapies.

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Mechanisms of regulation of liver fatty acid-binding protein

Cited by 9 publications

References 48 publications

The peroxisome proliferator-activated receptor regulates mitochondrial fatty acid oxidative enzyme gene expression.

The peroxisome proliferator-activated receptor regulates mitochondrial fatty acid oxidative enzyme gene expression.

Regulation of the Liver Fatty Acid Binding Protein Gene (L-FABP) by Hepatocyte NuclearFactor 1aplha: alterations in fatty acid homeostasis in HNF1alpha-deficient mice

Immune Mechanisms and Novel Pharmacological Therapies of Acute Kidney Injury

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