Liebl B, Mückter H, Doklea E, Fichtl B, Forth W
Walther-Straub-Institut für Pharmakologie and Toxikologie, Universität München, Germany.
Analyst. 1995 Mar;120(3):771-4. doi: 10.1039/an9952000771.
Trivalent monosubstituted organoarsenicals, e.g., oxophenylarsine (PhAsO), exert various detrimental effects on mammalian cells. In addition to their well known interference with pyruvate and ketoglutaric acid oxidation, the effect on other cellular functions such as uptake of glucose may contribute to their acute toxicity. Different effects of PhAsO on insulin-stimulated and insulin-independent uptake of hexoses in various tissues have been reported. It has been shown previously that PhAsO inhibits the stereospecific uptake of glucose in MDCK cells. In this work, the insulin dependence of glucose uptake in these cells and the effects of 2,3-dimercaptopropanol (BAL), dithiothreitol (DTT) and 2-mercaptoethanol (ME) on PhAsO-induced inhibition of glucose uptake were investigated. A 200 mumol l-1 concentration of insulin had no measurable effect on cellular 14C accumulation from D-[6(-14)C]glucose, indicating an insulin-independent hexose transport system. In the presence of 2 mumol l-(-1) of PhAsO, glucose uptake was lowered to less than 50% of controls within 30 min. Greater inhibition was observed with higher concentrations of PhAsO, but cell viability as assessed by formazan formation started to decrease at concentrations > or = to 5 mumol l-1, especially after longer exposure times. When BAL was added in a ten-fold molar excess 30 min after beginning incubation with PhAsO (2 mumol l-1, virtually complete recovery of inhibited glucose uptake occurred within 10 min after addition. ME at up to a 100-fold molar excess over arsenic had no influence on the inhibition of glucose uptake within 120 min after addition.(ABSTRACT TRUNCATED AT 250 WORDS)
三价单取代有机砷化合物，例如氧代苯胂（PhAsO），对哺乳动物细胞有多种有害影响。除了它们对丙酮酸和酮戊二酸氧化的众所周知的干扰外，对其他细胞功能如葡萄糖摄取的影响可能导致其急性毒性。已有报道PhAsO对各种组织中胰岛素刺激的和非胰岛素依赖性的己糖摄取有不同影响。先前已表明PhAsO抑制MDCK细胞中葡萄糖的立体特异性摄取。在这项工作中，研究了这些细胞中葡萄糖摄取的胰岛素依赖性以及2,3-二巯基丙醇（BAL）、二硫苏糖醇（DTT）和2-巯基乙醇（ME）对PhAsO诱导的葡萄糖摄取抑制的影响。200μmol l-1浓度的胰岛素对细胞从D-[6(-14)C]葡萄糖中积累14C没有可测量的影响，表明存在非胰岛素依赖性己糖转运系统。在存在2μmol l-(-1)的PhAsO时，30分钟内葡萄糖摄取降至对照的不到50%。在较高浓度的PhAsO下观察到更大的抑制作用，但通过甲臜形成评估的细胞活力在浓度≥5μmol l-1时开始下降，尤其是在较长暴露时间后。当在与PhAsO（2μmol l-1）孵育开始30分钟后以十倍摩尔过量添加BAL时，添加后10分钟内几乎完全恢复了被抑制的葡萄糖摄取。ME在超过砷的摩尔过量高达100倍时，在添加后120分钟内对葡萄糖摄取的抑制没有影响。（摘要截断于250字）
