Ramsammy L S, Boos C, Josepovitz C, Kaloyanides G J
Department of Medicine, State University of New York, Stony Brook 11794-8152.
Biochim Biophys Acta. 1993 Feb 23;1146(1):1-8. doi: 10.1016/0005-2736(93)90331-s.
The objective of this study was to determine whether streptozotocin-induced diabetes mellitus in the rat causes alterations in the lipid composition and fluidity of renal brush border membranes (BBM) and basolateral membranes (BLM). Compared to membranes of non-diabetic rats, BBM and BLM of diabetic rats contained 31% and 26%, respectively, less arachidonic acid and 36% and 46%, respectively, more linoleic acid esterfied in phospholipids. These changes were accompanied by a decrease in the average number of double bonds per mole of fatty acid, a measure of fatty acid unsaturation. In diabetic rats BLM had a higher total phospholipid/protein ratio (567 +/- 20 vs. 482 +/- 15 nmol/mg protein, P < 0.01), less cholesterol (369 +/- 30 vs. 512 +/- 34 nmol/mg protein, P < 0.01), more phosphatidylcholine (+72%) and less sphingomyelin (-22%) than did BBM. These differences were identical to those observed between BLM and BBM of non-diabetic rats. In control rats BLM was more fluid than BBM as assessed by the steady state fluorescence anisotrophy of diphenylhexatriene and by glycerol permeability. In diabetic rats the fluidity of BLM was not different from that of BBM as assessed by the steady state fluorescence anisotrophy of diphenylhexatriene whereas BLM was slightly more fluid than BBM as assessed by glycerol permeability. By both measures BLM and BBM from diabetic rats were significantly less fluid than BLM and BBM from control rats. Removal of proteins and cholesterol in sequence was accompanied by an increase in membrane fluidity in both groups. However, in no instance did the removal of proteins or cholesterol abolish the difference between the fluidity of diabetic membranes and that of control membranes. From these data we conclude that the reduction in fluidity of renal BLM and BBM in the diabetic rat is due to the change in the composition of fatty acids esterified in membrane phospholipids.
本研究的目的是确定链脲佐菌素诱导的大鼠糖尿病是否会导致肾刷状缘膜(BBM)和基底外侧膜(BLM)的脂质组成及流动性发生改变。与非糖尿病大鼠的膜相比,糖尿病大鼠的BBM和BLM中,磷脂酰化的花生四烯酸分别减少了31%和26%,亚油酸分别增加了36%和46%。这些变化伴随着每摩尔脂肪酸双键平均数的减少,这是脂肪酸不饱和度的一个指标。在糖尿病大鼠中,BLM的总磷脂/蛋白质比率更高(567±20对482±15 nmol/mg蛋白质,P<0.01),胆固醇含量更低(369±30对512±34 nmol/mg蛋白质,P<0.01),磷脂酰胆碱更多(+72%),鞘磷脂更少(-22%),与BBM相比。这些差异与非糖尿病大鼠的BLM和BBM之间观察到的差异相同。通过二苯基己三烯的稳态荧光各向异性和甘油通透性评估,在对照大鼠中,BLM比BBM更具流动性。通过二苯基己三烯的稳态荧光各向异性评估,在糖尿病大鼠中,BLM的流动性与BBM没有差异,而通过甘油通透性评估,BLM比BBM略具流动性。通过这两种测量方法,糖尿病大鼠的BLM和BBM的流动性明显低于对照大鼠的BLM和BBM。依次去除蛋白质和胆固醇后,两组的膜流动性均增加。然而,在任何情况下,去除蛋白质或胆固醇都没有消除糖尿病膜与对照膜流动性之间的差异。从这些数据中我们得出结论,糖尿病大鼠肾BLM和BBM流动性的降低是由于膜磷脂中酯化脂肪酸组成的变化。