CONTROL OF HEXOSE TRANSPORT IN CULTURED RETINOBLASTOMA

培养的视网膜母细胞瘤中己糖转运的控制

• 批准号: 3426437
• 负责人: HERMAN M KALCKAR
• 金额: $ 4.45万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-03-01 至 1990-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3426437
• 关键词: biological information processing; biological transport; blood brain barrier; cataract; chromatography; cow; galactose; glucose; glutamine; hexoses; laboratory rat; lens; pathology; radiotracer; retinoblastoma; spectrometry; tissue /cell culture; tunicamycin

The lens protein "crystalline" can be subject to various types of disorders. It is known that juvenile diabetes mellitus or various types of galactosemia bring about cataracts. The basis for these cataracts has often been ascribed to an entrapment of glucose or galactose by transport into the lens and subsequent enzymatic reduction into the corresponding polyols by the huge excess of sugar reductases. This state of affairs creates osmotic imbalance, due to the fact that the accumulating polyols seem not to have a facilitated efflux but have to diffuse out passively. The ensuing hyperosmosis would eventually draw water into the finely ordered crystalline of the lens and thus create a lens cataract. This seems to be the main factor in juvenile cataracts. What type of hexose transport system drives glucose or galactose into the lens and how is it regulated if at all? Hexose transport systems in fibroblast or myoblast cultures which can be downregulated by glucose are commonly observed. We shall call this down- regulation the transport "CURB". We have studied the transport curb in various lines of hamster lung fibroblast cultures. We obtained a particularly clear insight by using a mutant, the PGI mutant, because it lacks phospho-gluco-isomerase. This means that glucose-6-P cannot be converted to fructose-6-P a conversion which critical for the generation of aerobic energy metabolism which is essential for the transport curb. The PGI mutant shows a strong curb only with glucose, but not with mannose, glucosamine nor fructose. Surprisingly enough, the all- cis aldohexose, D-allose, turned out to be the most effective transport "curber"; D-altrose was inactive. Further progress depends on the availability of radiolabelled D-allose. Our finding that tunicamycin (TN) further intensifies the glucose or allose- induced curb (85% loss of transport capacity vs. fructose medium) is noteworthy so much the more since a switch from allose to fructose restores half the transport capacity within 6 hrs regardless of the presence or absence of TN. It would be of great interest to compare the hexose tansport systems of the lens with that of retina preps or cultures from retinablastoma, in regard to the mediated glucose-TN curb. A few hrs. preincubation followed by the usual transport test will be tried.

晶状体蛋白“结晶”可以受到各种类型的影响 失调。 众所周知，青少年糖尿病或各种 不同类型的半乳糖血症会导致白内障。 这些的基础 白内障通常归因于葡萄糖或 半乳糖通过运输进入晶状体并随后酶解 通过大量过量还原成相应的多元醇 糖还原酶。 这种状态会产生渗透性 不平衡，由于积累的多元醇似乎不 促进流出但必须被动扩散。 这 随后发生的高渗透压最终会将水吸入细水中 晶状体的晶体排列有序，从而形成晶状体白内障。 这似乎是青少年白内障的主要因素。 什么类型 己糖转运系统驱动葡萄糖或半乳糖进入 镜头以及它是如何监管的？ 己糖运输系统 成纤维细胞或成肌细胞培养物可以通过以下方式下调 经常观察到葡萄糖。 我们将称之为—— 监管交通“CURB”。 我们研究了交通 抑制仓鼠肺成纤维细胞培养物的各种品系。 我们 通过使用突变体 PGI 获得了特别清晰的见解 突变体，因为它缺乏磷酸葡萄糖异构酶。 这意味着 葡萄糖-6-P 不能转化为果糖-6-P a 对于有氧能量的产生至关重要的转换 新陈代谢对于运输限制至关重要。 地理标志协会 突变体仅对葡萄糖表现出强烈的抑制作用，但对葡萄糖则不然 甘露糖、葡萄糖胺或果糖。 令人惊讶的是，所有的—— 顺式己醛糖、D-阿洛糖被证明是最有效的 运输“路边”； D-阿卓糖没有活性。 进一步进展 取决于放射性标记的 D-阿洛糖的可用性。 我们的发现 衣霉素 (TN) 进一步强化葡萄糖或异糖- 诱导抑制（与果糖培养基相比，运输能力损失 85%） 自从从 allose 切换到 果糖在 6 小时内恢复一半的运输能力 无论是否存在 TN。 这将是伟大的 有兴趣比较透镜的己糖传输系统 视网膜制备物或视网膜母细胞瘤培养物，关于 介导的葡萄糖-TN 抑制。 几个小时。随后进行预孵育 通过通常的运输测试将被尝试。