Fatty acid binding protein 4/aP2-dependent BLT1R expression and signaling

Hertzel, Ann V.; Xu, Hong‐Liang; Downey, Michael; Kvalheim, Nicholas; Bernlohr, David A.

doi:10.1194/jlr.m074542

Cited by 18 publications

(14 citation statements)

References 72 publications

(98 reference statements)

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“…In proinflammatory M1 macrophages that accumulate in adipose tissue during obesity-linked metabolic diseases, UCP2 expression is blocked by adipocyte FA binding protein (FABP4/aP2), and the resulting release of redox signaling is involved in inflammasome activation and IL-1β secretion ( 161 , 385 ). Inflammasomes are cytoplasmic, multiprotein complexes involved in the sensing of danger signals, the role of which is to trigger caspase-1 activation and insufficient interleukin IL-1β maturation in response to diverse stimuli , sensed by pattern recognition receptors such as RIG-I-like receptors (sensing viral RNA), mitochondrial antiviral signaling protein, and TLR9 (sensing mtDNA).…”

Section: Involvement Of Ucps In Redox Homeostasis and Redox Regmentioning

confidence: 99%

Mitochondrial Uncoupling Proteins: Subtle Regulators of Cellular Redox SignalingReviewing Editors:Jerzy Beltowski, Joseph Burgoyne, Gabor Csanyi, Sergey Dikalov, Frank Krause, Anibal Vercesi, and Jeremy Ward

Ježek

Holendová

Garlid

et al. 2018

Antioxidants & Redox Signaling

100

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Significance: Mitochondria are the energetic, metabolic, redox, and information signaling centers of the cell. Substrate pressure, mitochondrial network dynamics, and cristae morphology state are integrated by the protonmotive force Δp or its potential component, ΔΨ, which are attenuated by proton backflux into the matrix, termed uncoupling. The mitochondrial uncoupling proteins (UCP1–5) play an eminent role in the regulation of each of the mentioned aspects, being involved in numerous physiological events including redox signaling.Recent Advances: UCP2 structure, including purine nucleotide and fatty acid (FA) binding sites, strongly support the FA cycling mechanism: UCP2 expels FA anions, whereas uncoupling is achieved by the membrane backflux of protonated FA. Nascent FAs, cleaved by phospholipases, are preferential. The resulting Δp dissipation decreases superoxide formation dependent on Δp. UCP-mediated antioxidant protection and its impairment are expected to play a major role in cell physiology and pathology. Moreover, UCP2-mediated aspartate, oxaloacetate, and malate antiport with phosphate is expected to alter metabolism of cancer cells.Critical Issues: A wide range of UCP antioxidant effects and participations in redox signaling have been reported; however, mechanisms of UCP activation are still debated. Switching off/on the UCP2 protonophoretic function might serve as redox signaling either by employing/releasing the extra capacity of cell antioxidant systems or by directly increasing/decreasing mitochondrial superoxide sources. Rapid UCP2 degradation, FA levels, elevation of purine nucleotides, decreased Mg2+, or increased pyruvate accumulation may initiate UCP-mediated redox signaling.Future Directions: Issues such as UCP2 participation in glucose sensing, neuronal (synaptic) function, and immune cell activation should be elucidated. Antioxid. Redox Signal. 29, 667–714.

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Section: Involvement Of Ucps In Redox Homeostasis and Redox Regmentioning

confidence: 99%

Mitochondrial Uncoupling Proteins: Subtle Regulators of Cellular Redox SignalingReviewing Editors:Jerzy Beltowski, Joseph Burgoyne, Gabor Csanyi, Sergey Dikalov, Frank Krause, Anibal Vercesi, and Jeremy Ward

Ježek

Holendová

Garlid

et al. 2018

Antioxidants & Redox Signaling

100

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“…Eosinophils, through the release of various mediators, including leukotrienes, are crucial for mucus secretion in the airways and in the development of AHR (39,41). FABP4 has been shown to stabilize LTA 4 toward chemical hydrolysis, thus favoring LTC 4 synthesis (29,72), and studies have shown that LTC 4 induces chemotaxis of eosinophils and expression of the adhesion molecule Mac-1 (␣M␤2-integrin) (16). Thus absence of FABP4 is likely to contribute to the reduced levels of LTC 4 in the lungs of allergen-challenged FABP4-deficient mice, which in turn can lead to reduced eosinophil recruitment to the airways.…”

Section: L237mentioning

confidence: 99%

“…It is predominantly a cytosolic protein, which is abundantly expressed in adipocytes and macrophages (15) and is secreted by adipocytes in response to cAMP (49). In adipocytes, FABP4 serves as a lipid chaperone and facilitates hormone-stimulated lipolysis (10), whereas, in macrophages, the protein stabilizes leukotriene A 4 to hydrolysis, thereby potentiating synthesis of cysteinyl leukotriene C4 (LTC 4 ) (29,72). Studies have also demonstrated FABP4 expression in other cell types, such as dendritic cells, epithelial cells, and endothelial cells under physiological and/or pathological conditions (18).…”

Section: Introductionmentioning

confidence: 99%

FABP4 regulates eosinophil recruitment and activation in allergic airway inflammation

Ge¹,

Baştan²,

Dileepan³

et al. 2018

American Journal of Physiology-Lung Cellular and Molecular Phys

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Fatty acid binding protein 4 (FABP4), a member of a family of lipid-binding proteins, is known to play a role in inflammation by virtue of its ability to regulate intracellular events such as lipid fluxes and signaling. Studies have indicated a proinflammatory role for FABP4 in allergic asthma although its expression and function in eosinophils, the predominant inflammatory cells recruited to allergic airways, were not investigated. We examined expression of FABP4 in murine eosinophils and its role in regulating cell recruitment in vitro as well as in cockroach antigen (CRA)-induced allergic airway inflammation. CRA exposure led to airway recruitment of FABP4-expressing inflammatory cells, specifically eosinophils, in wild-type (WT) mice. FABP4 expression in eosinophils was induced by TNF-α as well as IL-4 and IL-13. FABP4-deficient eosinophils exhibited markedly decreased cell spreading/formation of leading edges on vascular cell adhesion molecule-1 and significantly decreased adhesion to intercellular adhesion molecule-1 associated with reduced β2-integrin expression relative to WT cells. Furthermore, FABP4-deficient eosinophils exhibited decreased migration, F-actin polymerization, calcium flux, and ERK(1/2) phosphorylation in response to eotaxin-1. In vivo, CRA-challenged FABP4-deficient mice exhibited attenuated eosinophilia and significantly reduced airway inflammation (improved airway reactivity, lower IL-5, IL-13, TNF-α, and cysteinyl leukotriene C4 levels, decreased airway structural changes) compared with WT mice. In conclusion, expression of FABP4 in eosinophils is induced during conditions of inflammation and plays a proinflammatory role in the development of allergic asthma by promoting eosinophil adhesion and migration and contributing to the development of various aspects of airway inflammation.

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“…Studies have shown that FABP4 can enhance insulin sensitivity and reduce atherosclerosis. Knockdown of FABP4 gene can reduce the expression of inflammation-driven macrophage receptor (16). Ning et al (17), reported that FABP4 was overexpressed in GDM patients and has a significant positive correlation with IR and inflammatory factor TNF-α, suggesting that FABP4 can be used as a new biomarker for GDM.…”

Section: Introductionmentioning

confidence: 99%

Expression and correlation of Chemerin and FABP4 in peripheral blood of gestational diabetes mellitus patients

Wang

Liu²,

Wang

et al. 2019

Exp Ther Med

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Expression and correlation of Chemerin and fatty acid-binding protein 4 (FABP4) in peripheral blood of gestational diabetes mellitus (GDM) patients were investigated. Sixty patients with GDM from March 2018 to March 2019 in the People's Hospital of Zhangqiu Area were selected as the study group (SG) and another 50 healthy pregnant women corresponding to their age and pregnancy were selected as the control group (CG). Enzyme linked immunosorbent assay (ELISA) was used to detect the expression of Chemerin and FABP4 in serum. Receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of Chemerin and FABP4 in peripheral blood for GDM patients. Pearson's correlation coefficient was used to analyze the correlation between Chemerin and FABP4 and the correlation between Chemerin and inflammatory factors such as interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). Expression of Chemerin and FABP4 in peripheral blood of GDM patients were significantly higher than those in CG. The AUC of GDM patients diagnosed with Chemerin and FABP4 in peripheral blood was 0.820 and 0.814, while the AUC of GDM patients diagnosed with Chemerin combined with FABP4 in peripheral blood was 0.904. Expression of inflammatory factors IL-6 and TNF-α in the SG were significantly higher than those in the CG. Chemerin in the SG was positively correlated with FABP4 and positively correlated with inflammatory factors IL-6 and TNF-α. Patients with advanced age (≥35 years), family history of diabetes, hyperlipidemia, high pre-pregnancy BMI, high fasting blood glucose, high Chemerin and high FABP4 expression have high risk of GDM. In conclusion, Chemerin and FABP4 were upregulated in the peripheral blood of GDM patients. There was a positive correlation between the two and a positive correlation with the inflammatory factors IL-6 and TNF-α.

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Fatty acid binding protein 4/aP2-dependent BLT1R expression and signaling

Cited by 18 publications

References 72 publications

Mitochondrial Uncoupling Proteins: Subtle Regulators of Cellular Redox SignalingReviewing Editors:Jerzy Beltowski, Joseph Burgoyne, Gabor Csanyi, Sergey Dikalov, Frank Krause, Anibal Vercesi, and Jeremy Ward

Mitochondrial Uncoupling Proteins: Subtle Regulators of Cellular Redox SignalingReviewing Editors:Jerzy Beltowski, Joseph Burgoyne, Gabor Csanyi, Sergey Dikalov, Frank Krause, Anibal Vercesi, and Jeremy Ward

FABP4 regulates eosinophil recruitment and activation in allergic airway inflammation

Expression and correlation of Chemerin and FABP4 in peripheral blood of gestational diabetes mellitus patients

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