Glaesser D, Fass U, Gruner M, Thust O, Iwig M, Spindler M
Institute of Physiological Chemistry, Faculty of Medicine, Martin Luther University, Halle (Saale)/Germany.
Eur J Cell Biol. 1996 Nov;71(3):286-92.
As low as 5 micromol/l of cis-linoleic acid proves to be cytotoxic for bovine lens epithelial cells in culture. Albumin eliminates the linoleic acid cytotoxicity completely, presumably by binding the fatty acid. However, the damaging effect appears again when the molar ratio of linoleic acid to albumin exceeds 1:1. The assumption that the linoleic acid-caused cell damage would be mediated by peroxidation products could not be confirmed. The results obtained rather favor the idea that linoleic acid molecules themselves injure lens epithelial cells. Obviously, cell damage even occurs in the presence of albumin if one molecule of albumin binds more than one molecule of linoleic acid. Micromolar concentrations of linoleic acid produce reversible bleb formation as well as cell retraction within 30 min. In primary culture 10 micromol/l linoleic acid damage lens epithelial cells irreversibly within some hours. Trans-linoleic acid, linolenic acid and oleic acid are also harmful to lens cells but to a lesser degree, while saturated fatty acids are without any effect. Bleb formation as a leading early sign hints at the plasma membrane as the primary target for linoleic acid induced cytotoxicity.
低至5微摩尔/升的顺式亚油酸对培养中的牛晶状体上皮细胞具有细胞毒性。白蛋白可完全消除亚油酸的细胞毒性,推测是通过结合脂肪酸来实现的。然而,当亚油酸与白蛋白的摩尔比超过1:1时,损伤作用会再次出现。亚油酸导致细胞损伤由过氧化产物介导这一假设未能得到证实。所得结果更倾向于亚油酸分子本身会损伤晶状体上皮细胞这一观点。显然,如果一个白蛋白分子结合不止一个亚油酸分子,即使存在白蛋白,细胞也会受损。微摩尔浓度的亚油酸在30分钟内会产生可逆的气泡形成以及细胞收缩。在原代培养中,10微摩尔/升的亚油酸在数小时内会不可逆地损伤晶状体上皮细胞。反式亚油酸、亚麻酸和油酸对晶状体细胞也有危害,但程度较小,而饱和脂肪酸则没有任何影响。气泡形成作为主要的早期迹象表明质膜是亚油酸诱导细胞毒性的主要靶点。