ENHANCED STEROL SYNTHESIS IN CONCANAVALIN A-STIMULATED LYMPHOCYTES - CORRELATION WITH PHOSPHOLIPID-SYNTHESIS AND DNA-SYNTHESIS

ENHANCED STEROL SYNTHESIS IN CONCANAVALIN A-STIMULATED LYMPHOCYTES - CORRELATION WITH PHOSPHOLIPID-SYNTHESIS AND DNA-SYNTHESIS
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DOI:
10.1002/jcp.1041000115
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发表时间:
1979-01-01
影响因子:
5.6
通讯作者:
CHEN, SSH
CHEN, SSH
中科院分区:
生物学2区
文献类型:
--
作者:
CHEN, SSH

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在人淋巴细胞培养物中研究了(14 C)胆碱和(3 H)肌醇掺入总脂质部分、(14 C)乙酸酯掺入甾醇部分和(3 H)胸苷掺入DNA。伴刀豆球蛋白A诱导这些标记的掺入增加,具有以下特征:(a)磷脂合成迅速增加。甾醇合成和DNA合成增加的滞后时间分别为5小时和27小时;(B)磷脂合成和甾醇合成的增加与ConA浓度成正比。用高浓度ConA处理的细胞显示出非常低的DNA合成水平;(c)磷脂合成的增加可以立即被α-甲基-甘露糖苷消除。α-甲基-甘露糖苷钝化但不消除甾醇合成的增加。α-甲基-甘露糖苷增强了高浓度ConA处理的细胞的DNA合成;(d)用25-羟基胆固醇选择性抑制甾醇合成不能阻止磷脂合成的增加,但它阻止了DNA合成的增加。向淋巴细胞培养物中补充LDL、HDL或总脂蛋白可有效防止25-羟基胆固醇对DNA合成的抑制。这些结果表明,在淋巴细胞活化的刀豆蛋白A磷脂合成,甾醇合成和DNA合成依次增加。有丝分裂的细胞承诺率与ConA浓度成正比。高浓度的ConA在G1期的后承诺点阻止细胞生长。增强磷脂合成是一个承诺前的事件。增强的甾醇合成是一个postcommitment事件,反映了通过G1细胞生长的胆固醇供应增加的要求。
Incorporation of (14C)choline and (3H)myo‐inositol into the total lipid fraction, incorporation of (14C)acetate into the sterol fraction and incorporation of (3H)thymidine into DNA were studied in human lymphocyte cultures. Concanavalin A induced an increase in the incorporation of these labels with the following features: (a) Phospholipid synthesis was increased promptly. The lag time for the increase in sterol synthesis and DNA synthesis were 5 hours and 27 hours respectively; (b) The increase in phospholipid synthesis and sterol synthesis was proportional to ConA concentration initially. Cells treated with a high concentration of ConA showed very low levels of DNA synthesis; (c) The increase in phospholipid synthesis could be abolished immediately by α‐Methyl‐Mannoside. α‐Methyl‐Mannoside blunted but did not abolish the increase in sterol synthesis. α‐Methyl‐Mannoside enhanced DNA synthesis of those cells which had been treated by a high concentration of ConA; and (d) Selective inhibition of sterol synthesis with 25‐hydroxycholesterol did not prevent the increase in phospholipid synthesis, but it blocked the increase in DNA synthesis. Supplement of LDL, HDL or total lipoproteins to lymphocyte cultures was effective in preventing the inhibition of DNA synthesis by 25‐hydroxycholesterol. These results suggest that in lymphocyte activation by ConA phospholipid synthesis, sterol synthesis and DNA synthesis were sequentially increased. The rate of cellular commitment to mitogenesis was proportional to ConA concentrations. High concentrations of ConA arrested the cell growth at a postcommitment point in the G1 phase. Enhanced phospholipid synthesis was a precommitment event. Enhanced sterol synthesis was a postcommitment event and reflected the requirement of an increased cholesterol supply for the passage of cell growth through G1.