Hrelia S, Bordoni A, Caboni M F, Lercker G, Capella P, Turchetto E, Biagi P
Dipartimento di Biochimica, Università di Bologna, Italy.
Biochem Mol Biol Int. 1994 Mar;32(3):565-73.
In order to evaluate the effect of one of the main oxysterols derived from cholesterol oxidation, cholesterol-5 alpha,6 alpha-epoxide (epox), on cardiac cells, we have supplemented the culture medium of neonatal rat cardiomyocytes with scalar concentrations of epox (0.1-100 microM). While 0.1 microM epox supplementation was ineffective, epox supplementation in the range 1-100 microM determined a reduction in cellular protein level, without affecting cell viability, and a dose-dependent epox incorporation into cardiomyocyte lipids. Furthermore, in the same concentration range of epox supplementation, a gas chromatographic peak unambiguously identified by gas chromatography-mass spectrometry as cholestane-3 beta,5 alpha,6 beta-triol, an hydrolytic metabolite of epox, was detected. The mechanism of cytotoxicity of epox to cardiomyocytes could be due to the insertion of epox itself into cellular lipids, and to its metabolization to the more toxic triol.
为了评估胆固醇氧化产生的主要氧化甾醇之一胆固醇-5α,6α-环氧化物（环氧物）对心脏细胞的影响，我们用不同浓度（0.1 - 100微摩尔）的环氧物补充新生大鼠心肌细胞的培养基。虽然补充0.1微摩尔环氧物无效，但补充1 - 100微摩尔环氧物会导致细胞蛋白水平降低，而不影响细胞活力，且环氧物以剂量依赖的方式掺入心肌细胞脂质中。此外，在相同的环氧物补充浓度范围内，通过气相色谱 - 质谱法明确鉴定出一个气相色谱峰，其为环氧物的水解代谢产物胆甾烷-3β,5α,6β-三醇。环氧物对心肌细胞的细胞毒性机制可能是由于环氧物本身插入细胞脂质中，以及其代谢为毒性更强的三醇。
