Search results for APOA1

Showing 12 results out of 34

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Protein (6 results from a total of 12)

Identifier: R-HSA-2429641
Species: Homo sapiens
Compartment: early endosome
Primary external reference: UniProt: APOA1: P02647
Identifier: R-HSA-2395781
Species: Homo sapiens
Compartment: cytosol
Primary external reference: UniProt: APOA1: P02647
Identifier: R-HSA-350761
Species: Homo sapiens
Compartment: secretory granule lumen
Primary external reference: UniProt: APOA1: P02647
Identifier: R-HSA-8957081
Species: Homo sapiens
Compartment: endoplasmic reticulum lumen
Primary external reference: UniProt: APOA1: P02647
Identifier: R-HSA-976865
Species: Homo sapiens
Compartment: extracellular region
Primary external reference: UniProt: APOA1: P02647
Identifier: R-HSA-6806968
Species: Homo sapiens
Compartment: mitochondrial matrix
Primary external reference: UniProt: NAXE: Q8NCW5

Reaction (6 results from a total of 14)

Identifier: R-HSA-216723
Species: Homo sapiens
Compartment: plasma membrane
In an ATP-dependent reaction, ATP-binding cassette sub-family A member 1 (ABCA1, ATPA1) mediates the movement of intracellular cholesterol to the extracellular face of the plasma membrane. Cholesterol associated with cytosolic vesicles is a substrate for this reaction. Under physiologocal conditions, the active form of ABCA1 is predominantly a tetramer associated with apolipoprotein A-I (APOA1) (Denis et al. 2004; Vedhachalam et al., 2007). The number of lipid molecules transported per ATP consumed is not known.
Identifier: R-HSA-5682111
Species: Homo sapiens
Compartment: plasma membrane, cytosol, transport vesicle membrane
In an ATP-dependent reaction, ATP-binding cassette sub-family A member 1 (ABCA1) mediates the movement of intracellular cholesterol (CHOL) to the extracellular face of the plasma membrane. Cholesterol associated with cytosolic vesicles is a substrate for this reaction. Under physiologocal conditions, the active form of ABCA1 is predominantly a tetramer, which is post-translationally modified (palmitoylated and phosphorylated) and is associated with apolipoprotein A-I (APOA1). Defects in ABCA1 can cause Tangier disease (TGD; MIM:205400 aka high density lipoprotein deficiency type 1), an autosomal recessive disorder characterised by significantly reduced levels of plasma high density lipoproteins (HDL) resulting in tissue accumulation of cholesterol esters. Low HDL levels are among the most common biochemical abnormalities observed in coronary heart disease (CHD) patients. Mutations causing TGD include C1417R, Q537R, S1446L, N935S, W590S and R587W (Brooks-Wilson et al. 1999, Lapicka-Bodzioch et al. 2001, Guo et al. 2002, Tanaka et al. 2003).
Identifier: R-HSA-9618394
Species: Homo sapiens
Compartment: nucleoplasm, cytosol
The ADP-ribosylation factor-like protein 4C (ARL4C, also known as ARL7) gene is transcribed to yield mRNA. Cholesterol-loading or treatment with the synthetic agonists of liver X-receptors alpha (LXRα, NR1H3) and beta (LXRβ, NR1H2), such as T0901317 or GW3965, significantly induced the expression of ARL4C in murine RAW 264.7 and human THP1 macrophage cell lines (Hong C et al. 2011; Engel T et al. 2004; Sun D et al. 2012). Transcriptional studies of primary macrophages from single and double knockout NR1H2 or NR1H3 mice treated with LXR ligands GW3965 or T0901317 revealed that both receptors independently regulate ARL4C and induction was abolished only in the absence of both receptors (Hong C et al. 2011). Induction of ARL4C mRNA expression by NR1H2 or NR1H3 agonist was preserved in the presence of cycloheximide, indicating that new protein synthesis is not required for the effect of LXRs on ARL7. Similar regulation of ARL4C mRNA expression was observed in human peripheral blood-derived monocytes (Hong C et al. 2011). NR1H2 or NR1H3 stimulation of ARL4C has been shown to transport cholesterol to the membrane for the ATP-binding cassette transporter A1 (ABCA1)-associated cholesterol removal (Engel T et al. 2004). Overexpression of ARL4C in HeLa cells enhances APOA1-mediated cholesterol efflux (Engel T et al. 2004).
Identifier: R-HSA-9618405
Species: Homo sapiens
Compartment: cytosol, plasma membrane
The ADP-ribosylation factor-like 4C (ARL4C or ARL7) mRNA is translated to yield ARL4C protein. ARL4C localizes to both the cell surface membrane and nucleus; however, a GDP-restricted mutant (Arl4c T27N) is mainly distributed in the cytoplasm (Engel T et al. 2004; Heo WD et al. 2006). Further, mutant constructs showed that effective plasma membrane targeting of ARL4C required an N-terminal myristoyl motif as well as a flexible C-terminal polybasic tail, which suggests that the two ends of the protein synergistically support cell surface targeting (Heo WD et al. 2006).

Cholesterol-loading or treatment with the synthetic agonists of liver X-receptors alpha (LXRα, NR1H3) and beta (LXRβ, NR1H2), such as T0901317 or GW3965, significantly induced the expression of ARL4C in murine RAW 264.7 and human THP1 macrophage cell lines (Hong C et al. 2011; Engel T et al. 2004; Sun D et al. 2012). Similar regulation of ARL4C mRNA expression was observed in human peripheral blood-derived monocytes (Hong C et al. 2011). NR1H2 or NR1H3 stimulation ARL4C has been shown to transport cholesterol to the membrane for the ATP-binding cassette transporter A1 (ABCA1)-associated cholesterol removal (Engel T et al. 2004). Overexpression of ARL4C in HeLa cells has been shown to enhance APOA1-mediated cholesterol efflux (Engel T et al. 2004). MicroRNA miR-26 represses NR1H2,3-dependent cholesterol efflux by targeting ARL4C mRNA (Sun D et al. 2012).

Identifier: R-HSA-9605057
Species: Homo sapiens
Compartment: nucleoplasm, plasma membrane
The ATP-binding cassette transporter A1 (ABCA1) gene is transcribed to yield mRNA.

T0901317 or GW3965, two synthetic agonists of liver X-receptors (LXRα, NR1H3 and LXRβ, NR1H2) or cholesterol-loading significantly induced the expression of ABCA1 mRNA in mouse RAW 264.7 and human THP1 macrophage cell lines (Costet P et al. 2000; Venkateswaran A et al. 2000; Whitney KD et al. 2001; Jakobsson T et al. 2009). Similar regulation of ABCA1 mRNA expression by NR1H2, 3 agonists was observed in human peripheral blood-derived monocytes (Larrede S et al. 2009). Treatment with T0901317 increased expression of ABCA1 mRNA in variety of cells and tissues isolated from wild type but not LXR-/- mice (lacking both NR1H3 and NR1H2) (Repa JJ et al. 2000; Wagner BL et al. 2003). At the same time, NR1H2, 3 repressed basal expression of ABCA1 in a tissue-specific manner, occurring in macrophages and intestinal mucosa but not in several other mouse tissues (Wagner BL et al. 2003). Treatment of human THP-1 macrophages with endogenous (25-hydroxycholesterol) or synthetic (T0901317) ligands of NR1H2,3 stimulated both transcriptional and posttranscriptional events to enhance ABCA1 expression (Ignatova ID et al. 2013). NR1H2,3-induced expression of ABCA1 is thought to promote ABCA1-mediated cellular cholesterol transport across the plasma membrane to lipid-poor apolipoproteins, such as ApoA1 and ApoE in the generation of nascent high-density lipoproteins (HDL) particles (Ignatova ID et al. 2013; Vedhachalam C et a. 2007). Loss of ABCA1 in humans results in Tangier disease, a condition in which patients have extremely low levels of circulating HDL, massive accumulation of cholesterol in macrophages, and an increased risk for developing atherosclerosis (Rust S et al. 1999).

Multiple microRNAs have been identified as regulators of ABCA1 mRNA levels (Horie T et al. 2010; Sun D et al. 2012; de Aguiar Vallim TQ et al. 2013).

Identifier: R-HSA-9657791
Species: Homo sapiens
Compartment: cytosol
Expression of the ATP-binding cassette transporter A1 (ABCA1) gene is induced by oxysterol-activated transcription factors liver X receptor α (LXRα, NR1H3) and LXRβ (NR1H2) and their heterodimeric partners, retinoid X receptors (RXR) via functional LXR response element (LXRE) (Costet P et al. 2000; Ignatova ID et al. 2013). NR1H2, 3-induced expression of ABCA1 is thought to promote ABCA1-mediated cellular cholesterol transport across the plasma membrane to lipid poor apolipoproteins, such as ApoA1 and ApoE in the generation of nascent HDL particles (Vedhachalam C et a. 2007; Ignatova ID et al. 2013). MicroRNA (miR-144) was found to bind the 3'-untranslated region (3'UTR) of ABCA1 mRNA to prohibit translation and reduce ABCA1-mediated cholesterol efflux from hepatocytes (de Aguiar Vallim TQ et al. 2013). In the liver, the farnesoid X receptor (FXR or NR1H4) often acts in opposition to LXRs in the regulation of cholesterol homeostasis. Indeed, FXR activation increases miR-144 expression to decrease hepatic ABCA1 levels and reduce circulating HDL concentrations in mouse models (de Aguiar Vallim TQ et al. 2013). Further, overexpression of miR-144 in a human hepatoma cell line (Hep3B) resulted in a decrease in both ABCA1 protein and efflux of cholesterol to lipid-poor ApoA-I, in the absence of a change in ABCA1 mRNA (de Aguiar Vallim TQ et al. 2013). Hepatic ABCA1 activity is responsible for ~75% of circulating HDL levels (with adipose and intestine contributing to the remainder). While macrophage ABCA1 activity is important in limiting foam cell formation during atherogenesis, macrophage ABCA1-generated HDL particles are not sufficiently abundant to significantly impact the circulating HDL pool. Of note, FXR is not expressed in macrophages, thus FXR/miR-144 is unlikely to contribute greatly to foam cell formation in atherogenesis, but FXR/miR-144 will more dramatically alter circulating serum HDL concentrations through its actions in the liver (de Aguiar Vallim TQ et al. 2013).
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