期刊
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
卷 301, 期 4, 页码 C886-C894出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpcell.00042.2011
关键词
RAW macrophage; BHK cells; CD39; apyrase; apolipoprotein A-I; ATP-binding cassette protein 1
资金
- Heart & Stroke Foundation of Ontario [T6384]
- Heart and Stroke Foundation of Canada-AstraZeneca
- Natural Sciences and Engineering Research Council of Canada
Lee JY, Karwatsky J, Ma L, Zha X. ABCA1 increases extracellular ATP to mediate cholesterol efflux to ApoA-I. Am J Physiol Cell Physiol 301: C886-C894, 2011. First published June 22, 2011; doi:10.1152/ajpcell.00042.2011.-ATP-binding cassette protein A1 (ABCA1) is a key plasma membrane protein required for the efflux of cellular cholesterol to extracellular acceptors, particularly to apolipoprotein A-I (apoA-I). This process is essential to maintain cholesterol homeostasis in the body. The detailed molecular mechanisms, however, are still insufficiently understood. Also, the molecular identity of ABCA1, i.e., channel, pump, or flippase, remains unknown. In this study we analyzed extracellular ATP levels in the medium of ABCA1-expressing BHK cells and RAW macrophages and compared them to the medium of nonexpressing cells. We found that extracellular ATP concentrations are significantly elevated when cells express ABCA1. Importantly, a dysfunctional ABCA1 mutant (A937V), when expressed similarly as wild-type ABCA1, is unable to raise extracellular ATP concentration, which suggests a casual relationship between functional ABCA1 and elevated extracellular ATP. To explore the physiological role of extracellular ATP, we analyzed ABCA1-mediated cholesterol efflux under conditions where extracellular ATP levels were modulated. We found that increasing extracellular ATP within the physiological range, i.e.,
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