Oxysterol-induced cell death in human leukemic T-cells correlates with oxysterol binding protein occupancy and is independent of glucocorticoid-induced apoptosis.
Oxysterol-induced cell death in human leukemic T-cells correlates with oxysterol binding protein occupancy and is independent of glucocorticoid-induced apoptosis.
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人类白血病 T 细胞中氧甾醇诱导的细胞死亡与氧甾醇结合蛋白的占据相关，并且与糖皮质激素诱导的细胞凋亡无关。
DOI：
10.1016/0960-0760(93)90096-f
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发表时间：
1993
期刊：
影响因子：
--
通讯作者：
Thompson,EB
中科院分区：
文献类型：
--
作者：
Bakos,JT;Johnson,BH;Thompson,EB
在真核细胞中，氧甾醇抑制胆固醇生物合成和细胞生长。使用强效氧甾醇（25-羟基胆固醇）研究氧甾醇对糖皮质激素敏感或耐药 CEM 细胞（人白血病 T 淋巴细胞）的三个克隆系的生物效应。此外，还测试了抗氧甾醇 CEM 细胞系的糖皮质激素敏感性。无论糖皮质激素如何反应，氧甾醇都会阻碍细胞生长并导致细胞裂解。本文研究的所有细胞都具有对 25-羟基胆固醇具有高亲和力的氧甾醇结合蛋白。对于在无血清培养基中生长的所有克隆，25-羟基胆固醇的半最大溶细胞浓度 (20-40 nM) 与其对该氧甾醇结合蛋白的亲和力 (Kd= ~ 31 nM) 相关。胆固醇和甲羟戊酸均可逆转 25-羟基胆固醇的细胞毒性； 3–6 μM 胆固醇或 0.1 mM 甲羟戊酸可将 60 nM 25-羟基胆固醇的细胞毒性降低 50%。即使在 60 nM 氧化甾醇治疗几天后，这种胆固醇或甲羟戊酸的逆转似乎也是可能的。胆固醇的保护作用可以通过增加 25-羟基胆固醇的浓度来克服。胆固醇和甲羟戊酸不能阻止糖皮质激素介导的淋巴细胞溶解作用。此外，氧甾醇抗性株系对地塞米松裂解敏感。这些数据支持氧甾醇和糖皮质激素独立作用以阻止人类白血病淋巴母细胞生长的假设。
In eukaryotic cells oxysterols inhibit cholesterol biosynthesis and cell growth. A potent oxysterol, 25-hydroxycholesterol, was used to investigate the biological effects of oxysterols on three clonal lines of either glucocorticoid-sensitive or -resistant CEM cells, human leukemic T-lymphocytes. In addition, the glucocorticoid sensitivity of an oxysterol-resistant CEM cell line was tested. Oxysterols blocked growth and caused the lysis of cells regardless of their glucocorticoid response. All cells studied herein possessed an oxysterol binding protein with high affinity for 25-hydroxycholesterol. For all clones grown in serum-free medium, the half-maximal cytolytic concentration of 25-hydroxycholesterol (20–40 nM) correlated with its affinity (Kd= ∼ 31 nM) for this oxysterol binding protein. Both cholesterol and mevalonate reversed 25-hydroxycholesterol cytotoxicity; 3–6 μM cholesterol or 0.1 mM mevalonate decreased 60 nM 25-hydroxycholesterol cytotoxicity by 50%. This cholesterol or mevalonate reversal appeared possible even after several days of 60 nM oxysterol treatment. The protective effect of cholesterol could be overcome by increasing 25-hydroxycholesterol concentrations. Cholesterol and mevalonate did not prevent glucocorticoid-mediated lymphocytolysis. Furthermore, the oxysterol-resistant line was sensitive to dexamethasone lysis. These data support the hypothesis that oxysterols and glucocorticoids act independently to block the growth of human leukemic lymphoblasts.
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影响因子：
2.5
作者：
DALSGAARD, CJ;VINCENT, SR;CUELLO, AC
通讯作者：
CUELLO, AC
狗长期离体腰骶脊髓的功能和结构
影响因子：
2.5
作者：
S. S. Tower
通讯作者：
S. S. Tower
影响因子：
4.1
作者：
NASHOLD, BS;FRIEDMAN, H
通讯作者：
FRIEDMAN, H
猴子脊髓的内在机制和运动机制的分离
影响因子：
2.5
作者：
S. S. Tower;D. Bodian;H. Howe
通讯作者：
H. Howe
DOI：
10.1126/science.7444459
发表时间：
1981
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Langford,LA;Coggeshall,RE
通讯作者：
Coggeshall,RE