Aldose reductase activity in retinal and cerebral microvessels and cultured vascular cells.

Aldose reductase activity in retinal and cerebral microvessels and cultured vascular cells.
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发表时间:
1983-09
影响因子:
4.4
通讯作者:
A. Kennedy;R. Frank;S. Varma
A. Kennedy;R. Frank;S. Varma
中科院分区:
医学2区
文献类型:
--
作者:
A. Kennedy;R. Frank;S. Varma

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从牛视网膜和大脑皮层分离的微血管(主要是毛细血管),以及培养的牛视网膜毛细血管周细胞和猪和犬视网膜毛细血管内皮细胞含有明显的醛糖还原酶活性。这一结论是基于这些培养的细胞和血管碎片在低(0.1 mM)底物浓度下,在NADPH存在下,以及当视网膜周细胞和内皮细胞在富含葡萄糖或半乳糖的培养基中培养时,在高水平山梨糖醇或半乳糖醇的积累中,优先于D-葡萄糖醛酸还原DL-甘油醛的能力。牛视网膜和脑微血管中这些活动的定量相似性,以及这两组微血管氧化14 C标记葡萄糖的能力在C-1或C-6位置的标记的定量相似性,表明醛糖还原酶可能不是糖尿病视网膜病变的主要致病因素。这一结论的建议,因为,虽然这些代谢活动是相似的牛视网膜和脑微血管,只有视网膜微血管系统遭受重大的解剖和功能损伤糖尿病。然而,必须谨慎看待这一结论,因为我们尚未研究的其他代谢途径可能会被过量的糖醇改变,并且在视网膜和脑微血管中存在不同的活性;可能存在物种差异;并且尚未使用人类微血管进行类似的实验。
Isolated microvessels (primarily capillaries) from bovine retina and cerebral cortex, as well as cultured bovine retinal capillary pericytes and porcine and canine retinal capillary endothelial cells contain apparent aldose reductase activity. This conclusion is based on the ability of these cultured cells and vessel fragments to reduce DL-glyceraldehyde in preference to D-glucuronate at low (0.1 mM) substrate concentrations, in the presence of NADPH, and in the accumulation of high levels of sorbitol or galactitol when retinal pericytes and endothelial cells are cultured in media enriched in glucose or galactose. The quantitative similarities of these activities in bovine retinal and cerebral microvessels, as well as the quantitatively similar ability of these two sets of microvessels to oxidize 14C-labeled glucose with the label either in the C-1 or the C-6 position, suggests that aldose reductase may not be a major causal factor in diabetic retinopathy. This conclusion is suggested because, while these metabolic activities are similar in bovine retinal and cerebral microvessels, only the retinal microvasculature suffers major anatomic and functional damage in diabetes. This conclusion must be viewed with caution, however, because other metabolic pathways that we have not investigated may be altered by an excess of sugar alcohols, and be present in differing activities in retinal and cerebral microvessels; species differences may exist; and similar experiments have not been conducted using human microvessels.