Enhanced sterol synthesis in concanavalin A‐stimulated lymphocytes: Correlation with phospholipid synthesis and DNA synthesis

Journal of Cellular Physiology - Tập 100 Số 1 - Trang 147-157 - 1979
S. Shi-Hua Chen1
1Pathology Department, Stanford University and Palo Alto Veterans Administration Medical Center, Stanford, California 94305

Tóm tắt

AbstractIncorporation 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.

Từ khóa


Tài liệu tham khảo

Boyum A., 1968, Isolation of mononuclear cells and granulocytes from human blood, Scan. J. Clin. Lab. Invest., 21, 1

10.1172/JCI107989

Chen S. S‐H.1979Relationship between phosphatidylcholine biosynthesis and cellular commitment in concanavalin‐A‐stimulated lymphocytes.Exp. Cell Res. in press.

10.1073/pnas.72.5.1950

10.1016/0014-4827(77)90009-X

Curtiss L. K., 1976, Regulatory serum lipoproteins: Regulation of lymphocyte stimulation by a species of low density lipoprotein, J. Immunol., 116, 1452, 10.4049/jimmunol.116.5.1452

10.1016/0005-2760(69)90189-1

10.1016/0005-2760(71)90232-3

10.1016/S0021-9258(18)64849-5

10.1172/JCI103182

10.1016/0003-2697(64)90125-3

10.1084/jem.144.2.444

10.1073/pnas.71.10.4229

10.1016/S0021-9258(19)42218-7

Kandutsch A. A., 1969, Prevention of cyclic and Triton‐induced increased in hydroxymethylglutaryl coenzyme A reductase and sterol synthesis by puromycin, J. Biol. Chem., 244, 2299, 10.1016/S0021-9258(19)78226-X

10.1038/219172a0

10.1042/bj1460247

10.1016/0005-2760(73)90135-5

10.1084/jem.144.6.1494

10.1084/jem.146.6.1791

10.1146/annurev.bi.47.070178.003435

10.1111/j.1432-1033.1972.tb01821.x

10.1016/0005-2760(78)90101-7

10.1038/265741a0

10.1016/0014-4827(78)90283-5