Up-regulation of ATP Binding Cassette Transporter A1 Expression by Very Low Density Lipoprotein Receptor and Apolipoprotein E Receptor 2

Chen, Xinping; Guo, ZhongMao; Okoro, Emmanuel U.; Zhang, Hongfeng; Zhou, Lichun; Lin, Xinhua; Rollins, Allman T.; Hong, Yun–Chul

doi:10.1074/jbc.m111.310888

Cited by 34 publications

(39 citation statements)

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“…In addition to adipocytes, VLDLR is also expressed in immune cells, including macrophages (22,23), but it is not known whether it regulates adipose tissue remodeling in obesity. In this study, we investigated the role of VLDLR in obesityrelated adipose tissue inflammation and adipocyte-macrophage interaction.…”

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confidence: 99%

Very Low Density Lipoprotein Receptor (VLDLR) Expression Is a Determinant Factor in Adipose Tissue Inflammation and Adipocyte-Macrophage Interaction

Nguyen

Huan

Metrione

et al. 2014

Journal of Biological Chemistry

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Obesity is associated with adipose tissue remodeling, characterized by adipocyte hypertrophy and macrophage infiltration. Previously, we have shown that very low density lipoprotein receptor (VLDLR) is virtually absent in preadipocytes but is strongly induced during adipogenesis and actively participates in adipocyte hypertrophy. In this study, we investigated the role of VLDLR in adipose tissue inflammation and adipocyte-macrophage interactions in wild type and VLDLR-deficient mice fed a high fat diet. The results show that VLDLR deficiency reduced high fat diet-induced inflammation and endoplasmic reticulum (ER) stress in adipose tissue in conjunction with reduced macrophage infiltration, especially those expressing pro-inflammatory markers. In adipocyte culture, VLDLR deficiency prevented adipocyte hypertrophy and strongly reduced VLDL-induced ER stress and inflammation. Likewise, cultures of primary peritoneal macrophages show that VLDLR deficiency reduced lipid accumulation and inflammation but did not alter chemotactic response of macrophages to adipocyte signals. Moreover, VLDLR deficiency tempered the synergistic inflammatory interactions between adipocytes and macrophages in a co-culture system. Collectively, these results show that VLDLR contributes to adipose tissue inflammation and mediates VLDL-induced lipid accumulation and induction of inflammation and ER stress in adipocytes and macrophages.

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Very Low Density Lipoprotein Receptor (VLDLR) Expression Is a Determinant Factor in Adipose Tissue Inflammation and Adipocyte-Macrophage Interaction

Nguyen

Huan

Metrione

et al. 2014

Journal of Biological Chemistry

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“…[53][54][55] More recently, activation of the VLDL receptor and the apoE receptor 2 have also been shown to increase ABCA1 mRNA levels and protein expression, as well as cholesterol efflux to apoA-I. 56 Conversely, macrophage ABCA1 gene expression and the efflux of cholesterol to apoA-I are suppressed by members Figure 2. Biogenesis of spherical high-density lipoproteins (HDLs).…”

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Regulation of High-Density Lipoprotein Metabolism

Rye

Barter

2014

Circulation Research

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There is compelling evidence from human population studies that plasma levels of high-density lipoprotein (HDL) cholesterol correlate inversely with cardiovascular risk. Identification of this relationship has stimulated research designed to understand how HDL metabolism is regulated. The ultimate goal of these studies has been to develop HDL-raising therapies that have the potential to decrease the morbidity and mortality associated with atherosclerotic cardiovascular disease. However, the situation has turned out to be much more complex than originally envisaged. This is partly because the HDL fraction consists of multiple subpopulations of particles that vary in terms of shape, size, composition, and surface charge, as well as in their potential cardioprotective properties. This heterogeneity is a consequence of the continual remodeling and interconversion of HDL subpopulations by multiple plasma factors. Evidence that the remodeling of HDLs may impact on their cardioprotective properties is beginning to emerge. This serves to highlight the importance of understanding not only how the remodeling and interconversion of HDL subpopulations is regulated but also how these processes are affected by agents that increase HDL levels. This review provides an overview of what is currently understood about HDL metabolism and how the subpopulation distribution of these lipoproteins is regulated.

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“…86 Activation of apoE receptor 2 (apoER2) following treatment of mouse macrophages with human apoE3 significantly increased ABCA1 mRNA and protein levels via the activation of the PI3K-PKCζ-Sp1 signaling cascade. 85 Furthermore, in vivo activation of apoER2 on mouse brain capillaries by elevated levels of apoE in the brain parenchyma, as a result of methamphetamine treatment, increased the expression of ABCB1 and reduced the expression of ABCC1 at the brain capillaries through the apoE/apoE receptor-2/c-Jun N-terminal kinase 1/2 pathway. 86 Modulation of ABCA1 expression and/or activity is, thus, expected to influence apoE/Aβ interactions along with Aβ deposition and consequent undesirable effect in the brain.…”

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confidence: 99%

“…79 This study found that Aβ binding to apoE4 redirected the rapid clearance of free Aβ from LRP1 to the VLDL receptor, which internalized apoE4 and Aβ-apoE4 complex at the BBB more slowly than LRP1 compared to apoE2 and apoE3 and their Aβ complexes which cleared much faster via both VLDLR and LRP1. 79 Findings from recent studies have shown that apoE may play role in regulation of ABCA1 85 and the ABC transporters ABCB1 and ABCC1. 86 Activation of apoE receptor 2 (apoER2) following treatment of mouse macrophages with human apoE3 significantly increased ABCA1 mRNA and protein levels via the activation of the PI3K-PKCζ-Sp1 signaling cascade.…”

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Role of ABC Transporters in the Pathogenesis of Alzheimer’s Disease

Abuznait

Kaddoumi

2012

ACS Chem. Neurosci.

109

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Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the most common form of age-related dementia that begins with memory loss and progresses to include severe cognitive impairment. A major pathological hallmark of AD is the accumulation of beta amyloid peptide (Aβ) in senile plaques in the brain of AD patients. The exact mechanism by which AD takes place remains unknown. However, an increasing number of studies suggests that ATP-binding cassette (ABC) transporters, which are localized on the surface of brain endothelial cells of the bloodbrain barrier (BBB) and brain parenchyma, may contribute to the pathogenesis of AD. Recent studies have unraveled important roles of ABC transporters including ABCB1 (P-glycoprotein, P-gp), ABCG2 (breast cancer resistant protein, BCRP), ABCC1 (multidrug resistance protein 1, MRP1), and the cholesterol transporter ABCA1 in the pathogenesis of AD and Aβ peptides deposition inside the brain. Therefore, understanding the mechanisms by which these transporters contribute to Aβ deposition in the brain is important for the development of new therapeutic strategies against AD. This review summarizes and highlights the accumulating evidence in the literature which describe the role of altered function of various ABC transporters in the pathogenesis and progression of AD and the implications of modulating their functions for the treatment of AD. KEYWORDS: ABC transporters, Alzheimer's disease, blood-brain barrier, ABCA1, P-glycoprotein, MRP1, BCRP A lzheimer's disease (AD) is a progressive neurodegenerative disorder and the most common form of age-related dementia that begins with memory loss and progresses to include severe cognitive impairment.1 The pathogenesis of AD is complex, and involves molecular, genetic, cellular, and physiological alterations to the brain and blood-brain barrier (BBB) that are still not completely understood.2,3 The prevalence of AD is going up rapidly worldwide, with about 30 million people suffering from this disease nowadays, and it has an increasing socioeconomic impact. 4 Despite the huge demand for treatments, existing drugs have limited or no efficacy for AD. 5,6 AD is characterized by a significant loss of neurons and atrophy of the hippocampus and cerebral cortex.7 It begins as mild short-term memory disturbances and ends in total loss of cognition and executive functions.8−10 The neuropathology of AD is characterized by two pathogenic hallmarks: the intraneuronal neurofibrillary tangle (NFT) and the extracellular amyloid plaque. 11,12 NFTs are largely composed of hyperphosphorylated fibrillar forms of a protein called microtubule associated protein tau which accumulates in the entorhinal cortex and the pyramidal neurons of the CA1 region of the hippocampus and subiculum.7 The well-known amyloid cascade hypothesis suggests that AD is precipitated by the accumulation of amyloid plaques that are mainly composed of fibrils of peptides collectively known as beta amyloid (Aβ) which are produced by the sequential cleavage of am...

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Up-regulation of ATP Binding Cassette Transporter A1 Expression by Very Low Density Lipoprotein Receptor and Apolipoprotein E Receptor 2

Cited by 34 publications

References 39 publications

Very Low Density Lipoprotein Receptor (VLDLR) Expression Is a Determinant Factor in Adipose Tissue Inflammation and Adipocyte-Macrophage Interaction

Very Low Density Lipoprotein Receptor (VLDLR) Expression Is a Determinant Factor in Adipose Tissue Inflammation and Adipocyte-Macrophage Interaction

Regulation of High-Density Lipoprotein Metabolism

Role of ABC Transporters in the Pathogenesis of Alzheimer’s Disease

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