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在乙醇存在的情况下,分离的肝细胞对转铁蛋白中铁摄取的抑制是乙醇代谢的一种pH依赖性结果。

Depression of iron uptake from transferrin by isolated hepatocytes in the presence of ethanol is a pH-dependent consequence of ethanol metabolism.

作者信息

Beloqui O, Nunes R M, Blades B, Berk P D, Potter B J

出版信息

Alcohol Clin Exp Res. 1986 Aug;10(4):463-70. doi: 10.1111/j.1530-0277.1986.tb05125.x.

DOI:10.1111/j.1530-0277.1986.tb05125.x
PMID:3530028
Abstract

Incubation of freshly isolated rat hepatocytes with highly purified radiolabeled rat transferrin in weakly buffered medium in the presence of 10 mM ethanol resulted in a marked diminution of iron uptake by these cells, associated with a greater pH depression than in ethanol-free control studies. This effect on iron uptake persisted, even when the cells were preincubated for 90 min with ethanol before the addition of transferrin. Increasing the buffering capacity of the system or the addition of a metabolic inhibitor of alcohol dehydrogenase (4-methylpyrazole) returned iron uptake to control values. Acetaldehyde, acetate, lactate (products of ethanol metabolism), and 3-butanol (an alcohol not metabolized by alcohol dehydrogenase) had no influence on iron uptake. Further investigation of iron uptake over the pH range 6-8.5 revealed a marked dependency of iron uptake on the extracellular pH. Leucine incorporation into cell protein was also found to be pH dependent. It is suggested that, in the light of current understanding of transferrin recycling by other cell types, the disturbances of iron homeostasis observed in alcoholics can be partially accounted for by alterations in their acid-base metabolism.

摘要

在存在10 mM乙醇的弱缓冲培养基中,将新鲜分离的大鼠肝细胞与高度纯化的放射性标记大鼠转铁蛋白一起孵育,导致这些细胞对铁的摄取显著减少,与无乙醇对照研究相比,pH值下降更大。即使在添加转铁蛋白之前,细胞先用乙醇预孵育90分钟,这种对铁摄取的影响仍然存在。增加系统的缓冲能力或添加酒精脱氢酶的代谢抑制剂(4-甲基吡唑)可使铁摄取恢复到对照值。乙醛、乙酸、乳酸(乙醇代谢产物)和3-丁醇(一种不能被酒精脱氢酶代谢的醇)对铁摄取没有影响。在pH值6-8.5范围内对铁摄取的进一步研究表明,铁摄取明显依赖于细胞外pH值。还发现亮氨酸掺入细胞蛋白也依赖于pH值。根据目前对其他细胞类型转铁蛋白循环利用的理解,提示酗酒者中观察到的铁稳态紊乱可部分归因于其酸碱代谢的改变。

相似文献

1
Depression of iron uptake from transferrin by isolated hepatocytes in the presence of ethanol is a pH-dependent consequence of ethanol metabolism.在乙醇存在的情况下,分离的肝细胞对转铁蛋白中铁摄取的抑制是乙醇代谢的一种pH依赖性结果。
Alcohol Clin Exp Res. 1986 Aug;10(4):463-70. doi: 10.1111/j.1530-0277.1986.tb05125.x.
2
Iron uptake from transferrin by isolated hepatocytes: effect of ethanol.分离的肝细胞从转铁蛋白摄取铁:乙醇的影响。
Biochem Biophys Res Commun. 1984 Dec 14;125(2):824-30. doi: 10.1016/0006-291x(84)90613-2.
3
The effect of ethanol metabolism on ferritin uptake by freshly isolated rat hepatocytes: is acetaldehyde responsible for this alteration?乙醇代谢对新鲜分离的大鼠肝细胞摄取铁蛋白的影响:乙醛是这种改变的原因吗?
Alcohol Clin Exp Res. 1992 Apr;16(2):301-7. doi: 10.1111/j.1530-0277.1992.tb01381.x.
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Induction of transferrin receptor by ethanol in rat primary hepatocyte culture.乙醇对大鼠原代肝细胞培养中转铁蛋白受体的诱导作用。
Alcohol Clin Exp Res. 2004 Aug;28(8 Suppl Proceedings):98S-105S. doi: 10.1097/01.alc.0000133584.61304.19.
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Iron uptake from transferrin and asialotransferrin by hepatocytes from chronically alcohol-fed rats.长期酒精喂养大鼠肝细胞对转铁蛋白和去唾液酸转铁蛋白的铁摄取
Alcohol Clin Exp Res. 1992 Aug;16(4):810-5. doi: 10.1111/j.1530-0277.1992.tb00684.x.
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Transferrin and iron uptake by rat hepatocytes in culture.培养的大鼠肝细胞对转铁蛋白和铁的摄取
Am J Physiol. 1984 Jan;246(1 Pt 1):G26-33. doi: 10.1152/ajpgi.1984.246.1.G26.
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The effect of ethanol on the uptake, binding, and desialylation of transferrin by rat liver endothelium: implications in the pathogenesis of alcohol-associated hepatic siderosis.乙醇对大鼠肝内皮细胞转铁蛋白摄取、结合及去唾液酸化的影响:对酒精相关性肝铁质沉着症发病机制的启示
Am J Med Sci. 1991 May;301(5):299-304. doi: 10.1097/00000441-199105000-00001.
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Uptake of iron from transferrin by isolated hepatocytes. Relationship to cellular energy metabolism.分离的肝细胞从转铁蛋白摄取铁。与细胞能量代谢的关系。
Scand J Clin Lab Invest. 1986 Apr;46(2):107-13. doi: 10.3109/00365518609083645.
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Combined effects of ethanol and pH-change on protein synthesis in isolated rat hepatocytes.乙醇和pH变化对离体大鼠肝细胞蛋白质合成的联合作用。
Acta Pharmacol Toxicol (Copenh). 1981 Aug;49(2):134-40. doi: 10.1111/j.1600-0773.1981.tb00882.x.
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Uptake of iron from transferrin by isolated hepatocytes.
Biochim Biophys Acta. 1984 Jun 19;804(2):200-8. doi: 10.1016/0167-4889(84)90150-2.

引用本文的文献

1
Alcohol consumption impairs hepatic protein trafficking: mechanisms and consequences.饮酒损害肝脏蛋白质运输:机制和后果。
Genes Nutr. 2010 Jun;5(2):129-40. doi: 10.1007/s12263-009-0156-z. Epub 2009 Nov 5.
2
The role of transferrin in the mechanism of cellular iron uptake.转铁蛋白在细胞铁摄取机制中的作用。
Biochem J. 1990 Oct 1;271(1):1-9. doi: 10.1042/bj2710001.
3
Plasma membrane fatty acid-binding protein and mitochondrial glutamic-oxaloacetic transaminase of rat liver are related.大鼠肝脏的质膜脂肪酸结合蛋白与线粒体谷草转氨酶相关。
Proc Natl Acad Sci U S A. 1990 May;87(9):3484-8. doi: 10.1073/pnas.87.9.3484.