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Dominant cholesterol-metabolism ideas challenged by new research
Date:8/15/2007

testine for excretion or destruction.

The expression of PS on the cell's surface might be accomplished in one of two ways. First, the enzyme that transports PS into the cell -- aminophospholipid translocase -- might be inhibited or blocked by ABCA1, causing a passive build-up of PS on the cell surface. Alternatively, ABCA1 might activate or might actually be the enzyme, scramblase, which causes PS and other phospholipids to redistribute until there are equal amounts inside and outside the cell membrane, making it possible to load the phospholipids and cholesterol onto apoA1.

During programmed cell death (apoptosis), PS is also expressed on the surface of apoptotic cells to signal macrophages to come and clean up the dead cells. Both the macrophages and apoptotic cells must express PS on their surfaces for this mechanism to work normally. Therefore, Chimini also proposed that ABCA1 might be part of the molecular machinery involved in apoptosis and macrophage activity.

The Penn State-Amherst team performed a complex series of experiments to determine whether the ABCA1 enzyme is either actively involved in the transmembrane transport of phospholipids or regulates another enzyme that transports the phospholipids. They also examined the role of ABCA1 enzyme in apoptosis and macrophage activity.

A key part of the study was using cells from sufferers of a rare genetic disorder, Tangier disease, who lack the ABCA1 gene. For comparison, the team also studied cells from experimental mice in which the gene for ABCA1 has been knocked out.

Exacting measurements of the movement of various phospholipids across the membrane of normal cells showed that the rate of phospholipid transport into the cell is not affected by the presence or absence of the ABCA1 gene and its corresponding enzyme. Similar experiments with Tangier cells or knock-out mouse cells produced the same results. "This showed us,"
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Contact: Barbara K. Kennedy
science@psu.edu
814-863-4682
Penn State
Source:Eurekalert

Page: 1 2 3 4

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