Molecular Cloning of the Human ATP-Binding Cassette Transporter 1 (hABC1): Evidence for Sterol-Dependent Regulation in Macrophages

Langmann, Thomas; Klucken, Jochen; Reil, Markus; Liebisch, Gerhard; Luciani, Marie‐Françoise; Chimini, Giovanna; Kaminski, Wolfgang E.; Schmitz, Gerd

doi:10.1006/bbrc.1999.0406

Cited by 471 publications

(363 citation statements)

References 22 publications

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“…mRNA expression of these transporters/ receptor was determined in freshly isolated blood monocytes to determine their basal level in vivo, as ABCA1, ABCG1 and SR-BI might be altered during the differentiation of monocytes to macrophages in vitro. [23][24][25] In our preliminary experiments, protein expression of ABCA1, ABCG1 and SR-BI could hardly be detected by western blot. We only measured ABCA1 protein by FACS assay, and no suitable antibodies for ABCG1 and SR-BI were available.…”

Section: Abca1 Expression In Obesitymentioning

confidence: 72%

The expression of ATP-binding cassette transporter A1 in Chinese overweight and obese patients

Zhou

Wang

et al. 2009

Int J Obes

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Background: ATP-binding cassette transporters (ABCA1, ABCG1) and scavenger receptor class B type I (SR-BI) are the three most important cellular cholesterol transporters/receptor in regulating cholesterol efflux. We have investigated whether the expression of these transporters/receptor is altered in overweight and obese patients, and the potential association with the circulating adipokines. Methods: Adiponectin, leptin and resistin were assayed in two groups of healthy controls, overweight and obese patients. The expression of ABCA1, ABCG1 and SR-BI in monocytes was measured. Cholesterol efflux from monocyte-derived macrophages was also determined. Results: Circulating adiponectin was decreased, whereas leptin and resistin were increased in overweight and obese patients compared with healthy controls. ABCA1 expression was significantly decreased in overweight and obese patients (Po0.01), whereas the levels of ABCG1 and SR-BI were comparable between the two groups. Adiponectin was correlated with ABCA1 (r ¼ 0.44, Po0.001), but not with ABCG1 and SR-BI. No associations between leptin, resistin and the expression of ABCA1, ABCG1 and SR-BI were found. Cholesterol efflux from monocyte-derived macrophages to apolipoprotein AI or to autologous serum was significantly impaired in overweight and obese patients, which were correlated with ABCA1 expression (r ¼ 0.47, Po0.001; r ¼ 0.43, Po0.001, respectively). Conclusion: The expression of ABCA1 in monocytes is reduced in overweight and obese patients, and the reduction in ABCA1 is associated with the impairment of cholesterol efflux from monocyte-derived macrophages.

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Section: Abca1 Expression In Obesitymentioning

confidence: 72%

The expression of ATP-binding cassette transporter A1 in Chinese overweight and obese patients

Zhou

Wang

et al. 2009

Int J Obes

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“…12 An earlier connection between ABC1 and cellular cholesterol homeostasis was suggested by the demonstration that cholesterol-loading of macrophages by incubation with acetylated low-density lipoproteins resulted in up-regulation of ABC1 expression and that downregulation of ABC1 in macrophages followed HDL-mediated cholesterol depletion. 9 Moreover, cAMP-dependent regulation through phosphorylation of ABC1 12 correlated with increased cholesterol efflux induced by protein kinase A activation. 6,7 These observations, taken together with the association of mutations in ABC1 and Tangier disease, indicate that ABC1 plays a key role in cellular cholesterol trafficking.…”

Section: Commentsmentioning

confidence: 99%

“…Human ABC1 is an approximately 220-kd protein expressed in most tissues of body, but with the highest levels in placenta, liver, adrenal gland, lung, small intestine, and putamen. 9 Interestingly, the mouse ortholog of ABC1 was first shown to be involved in phagocytosis of apoptotic cells, 10 interleukin-1␤ secretion by macrophages, 11 and cAMP-regulated anion transport across plasma membranes. 12 An earlier connection between ABC1 and cellular cholesterol homeostasis was suggested by the demonstration that cholesterol-loading of macrophages by incubation with acetylated low-density lipoproteins resulted in up-regulation of ABC1 expression and that downregulation of ABC1 in macrophages followed HDL-mediated cholesterol depletion.…”

Section: Commentsmentioning

confidence: 99%

“…Recent studies in transgenic mice have strongly implicated SR-BI-mediated selective uptake of cholesterol by the liver as an important mechanism for clearance of plasma cholesterol into bile. 13 Accentuated expression in liver 9 makes ABC1 a similarly attractive subject for investigation with regard to a potential role in biliary cholesterol secretion. Although preliminary data have been presented that suggest biliary secretion of cholesterol is unaffected in abc1(Ϫ/Ϫ) mice, 14 an earlier study of biliary lipid secretion in a patient with Tangier disease showed reduced cholesterol secretion in the absence of changes in secretion of bile acids and phospholipids.…”

Section: Commentsmentioning

confidence: 99%

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Iron beware: A common HFE gene polymorphism may prevent the accurate molecular diagnosis of homozygous hemochromatosis in low-risk, but not high-risk groups

Press

2000

Hepatology

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“…25 This process might play an important role in enhancing flux of lipids from tissues. Given the expression of ABCA1 42 and PLTP 4 in the adipose tissue, such a transport mechanism could alternate lipid storage into adipocytes, which is the long-term process leading to obesity.…”

Section: Discussionmentioning

confidence: 99%

Haplotypes in the phospholipid transfer protein gene are associated with obesity-related phenotypes: the Québec Family Study

et al. 2005

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BACKGROUND:The phospholipid transfer protein (PLTP) may play a role in body fat regulation. OBJECTIVE: To investigate the association between PLTP genetic variants and obesity-related phenotypes. METHODS: Two intronic variants, one in intron 1 (c.À87G4A) and the other in intron 12 (c.1175 þ 68T4G), were genotyped in 811 participants of the Québec Family Study. Nine obesity-related phenotypes were investigated, including body mass index (BMI), obesity (BMIZ30 kg/m 2 ), and waist circumference, percentage of fat, fat mass and fat-free mass measured by hydrostatic weighing as well as total, visceral and subcutaneous abdominal adipose tissue areas assessed by computed tomography. Single markers and haplotypes were tested for associations in family-based designs using the FBAT program. RESULTS: The SNP located in intron 1 showed significant associations with obesity, BMI, waist circumference and fat-free mass (Po0.05). The low-frequency allele (A allele) was associated with higher trait values, suggesting that the transmission of this allele is associated with an increased risk of being obese. Significant associations were observed between haplotypes and obesity, waist circumference, percentage of fat and fat-free mass (Po0.05). The transmission of the AT haplotype (frequency ¼ 0.180) was positively associated with obesity-related phenotypes. After sequencing the promoter and the coding regions of the PLTP gene, we were unable to identify a mutation that could replicate these results. CONCLUSION: Intronic variants of the PLTP gene are significantly associated with obesity-related phenotypes. Considering the number and the relevance of candidate genes surrounding the PLTP locus and the absence of missense polymorphisms in the coding region, the associations could be mediated by a second gene allele in linkage disequilibrium with the marker locus.

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Molecular Cloning of the Human ATP-Binding Cassette Transporter 1 (hABC1): Evidence for Sterol-Dependent Regulation in Macrophages

Cited by 471 publications

References 22 publications

The expression of ATP-binding cassette transporter A1 in Chinese overweight and obese patients

The expression of ATP-binding cassette transporter A1 in Chinese overweight and obese patients

Iron beware: A common HFE gene polymorphism may prevent the accurate molecular diagnosis of homozygous hemochromatosis in low-risk, but not high-risk groups

Haplotypes in the phospholipid transfer protein gene are associated with obesity-related phenotypes: the Québec Family Study

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