Abstract
In erythrocytes and platelets, activation of a nonspecific lipid flipsite termed the scramblase allows rapid, bidirectional transbilayer movement of all types of phospholipids. When applied to lymphoid cells, scramblase assays reveal a similar activity, with scrambling rates intermediate between those seen in platelets and erythrocytes. Scrambling activity initiated in lymphoid cells by elevation of intracellular Ca(2+) proceeds after a lag not noted in platelets or erythrocytes. The rates of transbilayer movement of phosphatidylserine and phosphatidylcholine analogues are similar whether the scramblase is activated by elevated internal Ca(2+) or by apoptosis. Elevation of internal Ca(2+) levels in apoptotic cells does not result in an additive increase in the rate of lipid movement. In lymphoid cells from a patient with Scott syndrome, scramblase cannot be activated by Ca(2+), but is induced normally during apoptosis. These findings suggest that Ca(2+) and apoptosis operate through different pathways to activate the same scramblase.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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4-Chloro-7-nitrobenzofurazan / analogs & derivatives*
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4-Chloro-7-nitrobenzofurazan / metabolism
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Animals
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Apoptosis / genetics
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B-Lymphocytes / enzymology
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B-Lymphocytes / pathology
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Blood Coagulation Disorders / enzymology
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Blood Coagulation Disorders / genetics
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Blood Coagulation Disorders / pathology
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Calcium / metabolism
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Carrier Proteins / genetics
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Carrier Proteins / metabolism*
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Cell Line, Transformed
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Enzyme Activation / genetics
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Flow Cytometry
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Humans
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Hybridomas
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Jurkat Cells
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Lymphocytes / cytology
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Lymphocytes / enzymology*
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Membrane Proteins / genetics
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Membrane Proteins / metabolism*
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Mice
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Mutation
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Phosphatidylcholines / metabolism
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Phosphatidylserines / metabolism
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Phospholipid Transfer Proteins*
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Phospholipids / metabolism*
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Spectrometry, Fluorescence
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Syndrome
Substances
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1-acyl-2-(12-((7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)dodecanoyl)phosphatidylcholine
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Carrier Proteins
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Membrane Proteins
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Phosphatidylcholines
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Phosphatidylserines
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Phospholipid Transfer Proteins
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Phospholipids
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1-oleoyl-2-((N-(7-nitro-2,1,3-benzoxadiazol-4-yl)amino)caproyl)phosphatidylserine
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4-Chloro-7-nitrobenzofurazan
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Calcium