EARLY CHANGES IN INOSITOL LIPIDS AND THEIR METABOLITES INDUCED BY PLATELET-DERIVED GROWTH-FACTOR IN QUIESCENT SWISS MOUSE 3T3 CELLS
EARLY CHANGES IN INOSITOL LIPIDS AND THEIR METABOLITES INDUCED BY PLATELET-DERIVED GROWTH-FACTOR IN QUIESCENT SWISS MOUSE 3T3 CELLS
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DOI：
10.1042/bj2320099
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发表时间：
1985-01-01
影响因子：
4.1
通讯作者：
HASEGAWASASAKI, H
中科院分区：
文献类型：
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作者：
HASEGAWASASAKI, H
肌醇脂质周转进行了研究，在静止的瑞士小鼠3 T3细胞刺激血小板衍生生长因子（PDGF）。在37 ℃下用PDGF刺激细胞10分钟。（1）在[~（32）P]Pi预标记的细胞中，[~（32）P]磷脂酰肌醇4，5-二磷酸减少28%，[~（32）P]磷脂酰肌醇4-磷酸减少41%，磷脂酸的~（32）P标记增加1.7倍;（2）在用[~ 3 H]花生四烯酸预标记的细胞中，释放到培养基中的[~ 3 H]磷脂酸增加17.9倍，[~ 3 H]磷脂酰肌醇（PtdIns）减少20%，[~ 3 H]花生四烯酸增加8.6倍，培养基中[3 H]前列腺素E2增加57倍，释放到培养基中的[3 H]单酰基甘油增加5.3倍（最后一个被鉴定为2-酰基衍生物）;（3）在用[2- 3 H]甘油预标记的细胞中，[3 H]二酰基甘油增加1.7倍，[3 H]磷脂酸增加6.7倍，释放到培养基中的[3 H]溶血磷脂酰胆碱（lysoPtdCho）增加1.6倍，[3 H]PtdIns减少9%，[3 H]单酰基甘油增加1.6倍。PDGF刺激肌-[2- 3 H]肌醇预标记的细胞中肌醇三磷酸、二磷酸和单磷酸的形成。这些结果表明，在瑞士3 T3细胞刺激的PDGF，肌醇脂质水解产生的二酰基甘油部分降解为2-酰基甘油和部分转化为磷脂酸。lysoPtdCho的增加表明从刺激的细胞释放的花生四烯酸的一部分是通过用磷脂酶A2水解PtdCho形成的。在这项研究中使用的部分纯化的PDGF的半最大剂量的不同值被发现的各种反应的静止瑞士3 T3细胞PDGF。半最大剂量的值表明，激活一部分PDGF的细胞表面受体足以促进有丝分裂和细胞质游离Ca 2+浓度的增加，并且PGDF刺激的脂质代谢可能与PDGF激活的受体位点的数量成比例。
Inositol lipid turnover was studied in quiescent Swiss mouse 3T3 cells stimulated by platelet-derived growth factor (PDGF). Stimulation of the cells by PDGF for 10 min at 37.degree. C induced the following changes in lipids: (1) in cells prelabelled with [32P]Pi, a 28% decrease in [32P]phosphatidylinositol 4,5-bisphosphate, a 41% decrease in [32P]phosphatidylinositol 4-phosphate and a 1.7-fold increase in the 32P-labelling of phosphatidic acid; (2) in cells prelabelled with [3H8]arachidonic acid, a 17.9-fold increase in [3H]phosphatidic acid, a 20% decrease in [3H]phosphatidylinositol (PtdIns), an 8.6-fold increase in [3H]arachidonic acid released into the medium, a 57-fold increase in [3H]prostaglandin E2 in the medium, and a 5.3-fold increase in [3H]monoacylglycerol released into the medium (the last was identified as the 2-acyl derivative); (3) in cells prelabelled with [2-3H]glycerol, a 1.7-fold increase in [3H]diacylglycerol, a 6.7-fold increase in [3H]phosphatidic acid, a 1.6-fold increase in [3H]lysophosphatidylcholine (lysoPtdCho), a 9% decrease in [3H]PtdIns, and a 1.6-fold increase in [3H]monoacylglycerol released into the medium. PDGF stimulated the formation of inositol tris-, bis- and mono-phosphates in the cells prelabelled with myo-[2-3H]inositol. These results indicate that, in Swiss 3T3 cells stimulated by PDGF, diacylglycerol produced by the hydrolysis of inositol lipids is partly degraded to 2-acylglycerol and partly converted into phosphatidic acid. The increase in lysoPtdCho indicates that a portion of arachidonic acid released from the stimulated cells is formed by the hydrolysis of PtdCho with a phospholipase A2. Different values of half-maximal doses of the partially purified PDGF used in this study were found for the various responses of quiescent Swiss 3T3 cells to PDGF. The values for half-maximal doses suggest that activation of a fraction of the cell-surface receptor for PDGF is sufficient for mitogenesis and for an increase in the cytoplasmic free Ca2+ concentration, and that the PGDF-stimulated lipid metabolism is probably proportional to the number of receptor sites activated by PDGF.