Marinovich M, Guizzetti M, Ghilardi F, Paoletti R, Galli C L
Laboratory of Toxicology, Institute of Pharmacological Sciences, Milano, Italy.
Toxicology. 1995 May 5;99(1-2):125-34. doi: 10.1016/0300-483x(95)02993-i.
The cytotoxicity of 25-hydroxycholesterol, 26-hydroxycholesterol and its analogue, 26-aminocholesterol was investigated in murine epidermal cell line, HEL-30. Lactate dehydrogenase (LDH) leakage, protein synthesis and protein content were determined after exposure of cell monolayers to the compounds ranging from 0.1-200 microM for 2, 6, or 24 h. 26-Aminocholesterol affected all the parameters studied time and concentration dependently; 25-hydroxycholesterol and 26-hydroxycholesterol were not toxic for HEL-30 cells. The cellular target for 26-aminocholesterol was primarily the membrane, since the LDH leakage was already detectable 10 min after exposure. On the other hand, for the other two oxysterols a protective role on this structure might be postulated. In fact 25-hydroxycholesterol and 26-hydroxycholesterol decreased the natural LDH leakage due to the ageing of the culture. In addition, 20 microM 25-hydroxycholesterol reversed the effect of moderately lytic doses of 26-aminocholesterol and Triton X-100, but not of sodium dodecyl sulfate.
在小鼠表皮细胞系HEL-30中研究了25-羟基胆固醇、26-羟基胆固醇及其类似物26-氨基胆固醇的细胞毒性。将细胞单层暴露于浓度范围为0.1 - 200微摩尔的这些化合物中2、6或24小时后,测定乳酸脱氢酶(LDH)泄漏、蛋白质合成和蛋白质含量。26-氨基胆固醇对所研究的所有参数均有时间和浓度依赖性影响;25-羟基胆固醇和26-羟基胆固醇对HEL-30细胞无毒。26-氨基胆固醇的细胞靶点主要是细胞膜,因为暴露10分钟后即可检测到LDH泄漏。另一方面,对于其他两种氧化甾醇,可以推测它们对该结构具有保护作用。事实上,25-羟基胆固醇和26-羟基胆固醇降低了由于培养物老化导致的天然LDH泄漏。此外,20微摩尔的25-羟基胆固醇可逆转中等裂解剂量的26-氨基胆固醇和 Triton X-100的作用,但不能逆转十二烷基硫酸钠的作用。