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离体肝细胞中的再氧合损伤:细胞外ATP对阳离子稳态的影响

Reoxygenation injury in isolated hepatocytes: effect of extracellular ATP on cation homeostasis.

作者信息

Hayashi H, Chaudry I H, Clemens M G, Hull M J, Baue A E

出版信息

Am J Physiol. 1986 Apr;250(4 Pt 2):R573-9. doi: 10.1152/ajpregu.1986.250.4.R573.

DOI:10.1152/ajpregu.1986.250.4.R573
PMID:3963227
Abstract

The aims of this study were to determine 1) the effects of anoxia and reoxygenation on electrolytes and ATP content of isolated hepatocytes and 2) whether exogenous ATP-MgCl2 has any beneficial effects on the cellular alterations that are produced during the reoxygenation period. After 90 min anoxia, intracellular Na and inorganic phosphate (Pi) increased, K and ATP decreased, whereas Ca and Mg did not change. After 60 min of reoxygenation, intracellular Mg and Na levels decreased, Ca increased, and Pi levels returned to normal, but ATP levels remained low. These results suggest that the plasma membrane is relatively impermeable to divalent ions such as Ca2+, Mg2+, and HPO2-4 during anoxia but becomes permeable to them after reoxygenation. When anoxic cells were treated with ATP-MgCl2 during reoxygenation, intracellular ATP and Mg levels increased, but accumulation of Ca and Pi was also observed. Thus enhancement of Mg transport and specific stimulation of Ca-Pi sequestration occurs with ATP-MgCl2 treatment. Na and K levels exhibited biphasic reciprocal dose-response changes to ATP-MgCl2 treatment; i.e., 0.1 mM ATP-MgCl2 (low-dose) treatment increased K and decreased Na, whereas 1 mM ATP-MgCl2 (high-dose) treatment decreased K and increased Na. These results indicate that although addition of a single high-dose ATP-MgCl2 was deleterious over a period of 60 min, low-dose ATP-MgCl2 accelerates the recovery of postanoxic cellular electrolyte homeostasis.

摘要

本研究的目的是确定

1)缺氧和复氧对分离的肝细胞电解质和ATP含量的影响;2)外源性ATP-MgCl₂对复氧期产生的细胞改变是否有任何有益作用。缺氧90分钟后,细胞内Na和无机磷酸盐(Pi)增加,K和ATP减少,而Ca和Mg没有变化。复氧60分钟后,细胞内Mg和Na水平降低,Ca增加,Pi水平恢复正常,但ATP水平仍然较低。这些结果表明,缺氧期间质膜对Ca²⁺、Mg²⁺和HPO₂⁻₄等二价离子相对不渗透,但复氧后对它们变得可渗透。当缺氧细胞在复氧期间用ATP-MgCl₂处理时,细胞内ATP和Mg水平增加,但也观察到Ca和Pi的积累。因此,ATP-MgCl₂处理会增强Mg转运并特异性刺激Ca-Pi螯合。Na和K水平对ATP-MgCl₂处理呈现双相反向剂量反应变化;即,0.1 mM ATP-MgCl₂(低剂量)处理增加K并降低Na,而1 mM ATP-MgCl₂(高剂量)处理降低K并增加Na。这些结果表明,虽然在60分钟内添加单一高剂量的ATP-MgCl₂是有害的,但低剂量的ATP-MgCl₂可加速缺氧后细胞电解质稳态的恢复。

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引用本文的文献

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World J Gastroenterol. 2004 Mar 15;10(6):871-4. doi: 10.3748/wjg.v10.i6.871.
2
Alleviation of cyclosporine nephrotoxicity with verapamil and ATP-MgCl2. Mitochondrial respiratory and calcium studies.维拉帕米和ATP-MgCl₂减轻环孢素肾毒性。线粒体呼吸及钙研究。
Ann Surg. 1987 Nov;206(5):655-60. doi: 10.1097/00000658-198711000-00017.
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Late steady increase in cytosolic Ca2+ preceding hypoxic injury in hepatocytes.
肝细胞缺氧损伤前胞质Ca2+的晚期持续增加。
Biochem J. 1992 Apr 15;283 ( Pt 2)(Pt 2):399-402. doi: 10.1042/bj2830399.