Mechanism of extracellular ATP- and adenosine-induced apoptosis of cultured pulmonary artery endothelial cells.
Mechanism of extracellular ATP- and adenosine-induced apoptosis of cultured pulmonary artery endothelial cells.
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细胞外ATP和腺苷诱导培养肺动脉内皮细胞凋亡的机制。
DOI：
10.1152/ajplung.1998.275.2.l379
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发表时间：
1998
期刊：
影响因子：
--
通讯作者：
Cutaia,MV
中科院分区：
文献类型：
--
作者：
Rounds,S;Yee,WL;Dawicki,DD;Harrington,E;Parks,N;Cutaia,MV
细胞凋亡可能在加重内皮细胞损伤或限制内皮细胞增殖中起重要作用。我们已经发现细胞外的ATP(ExATP)和腺苷引起内皮细胞凋亡，并且细胞凋亡的发展与腺苷的细胞内代谢有关[Dawicki，D.D.，D.Chatterjee，J.Wyche和S.Rounds.Am.J·Physiol.273(肺细胞摩尔17)：1485-L494,1997年]。在本研究中，我们对这种效应的机制进行了探讨。我们发现外源性三磷酸腺苷、腺苷和腺苷-L-同型半胱氨酸水解酶抑制剂MDL-28842与未经处理的对照细胞相比，可引起细胞凋亡，并降低腺苷-L-蛋氨酸与同型半胱氨酸的比值。以可溶性[~3H]胸腺嘧啶核苷的释放作为DNA片段化的指标，我们发现腺苷与同型半胱氨酸共同孵育可增强腺苷对可溶性DNA释放的影响。这些结果提示外源性三磷酸腺苷和腺苷诱导内皮细胞凋亡的机制可能与抑制SAH水解酶有关。腺苷脱氨酶抑制剂可促进外源性ATP诱导的细胞凋亡，而腺苷脱氨酶抑制剂可部分抑制外源性腺苷诱导的细胞凋亡。这些结果提示腺苷脱氨酶可能也参与了腺苷诱导内皮细胞凋亡的机制。用荧光探针2′，7′-bis(2-carboxyethyl)-5(6)-carboxyfluorescein.评价腺苷和MDL-28842引起的细胞内酸中毒细胞外的氯喹可以预防腺苷诱导的酸中毒，但不能阻止细胞凋亡。因此，尽管细胞内酸中毒与腺苷诱导的细胞凋亡有关，但这种作用并不是必需的。我们推测外源性三磷酸腺苷和腺苷诱导内皮细胞凋亡可能是由于抑制了甲基转移酶(S)的活性。嘌呤诱导的内皮细胞凋亡可能是限制血管损伤后内皮细胞增殖的重要因素。
Apoptosis may be important in the exacerbation of endothelial cell injury or limitation of endothelial cell proliferation. We have found that extracellular ATP (exATP) and adenosine cause endothelial apoptosis and that the development of apoptosis is linked to intracellular metabolism of adenosine [Dawicki, D. D., D. Chatterjee, J. Wyche, and S. Rounds.Am. J. Physiol.273 (Lung Cell Mol. Physiol.17): L485–L494, 1997]. In the present study, we investigated the mechanism of this effect. We found that exATP, adenosine, and theS-adenosyl-l-homocysteine (SAH) hydrolase inhibitor MDL-28842 caused apoptosis and decreased the ratio ofS-adenosyl-l-methionine to SAH compared with untreated control cells. Using release of soluble [3H]thymidine as a measure of DNA fragmentation, we found that the effect of adenosine on soluble DNA release was potentiated by coincubation with homocysteine. These results suggest that the mechanism of exATP- and adenosine-induced endothelial cell apoptosis involves inhibition of SAH hydrolase. exATP-induced apoptosis was enhanced by an inhibitor of adenosine deaminase, whereas exogenous adenosine-induced apoptosis was partially inhibited by an adenosine deaminase inhibitor. These results suggest that adenosine deaminase may also be involved in the mechanism of adenosine-induced endothelial cell apoptosis. Adenosine and MDL-28842 caused intracellular acidosis as assessed with the fluorescent probe 2′,7′-bis(2-carboxyethyl)-5(6)-carboxyfluorescein. The cell-permeant base chloroquine prevented adenosine-induced acidosis but not apoptosis. Thus, although intracellular acidosis is associated with adenosine-induced apoptosis, it is not necessary for this effect. We speculate that exATP- and adenosine-induced endothelial cell apoptosis may be due to an inhibition of methyltransferase(s) activity. Purine-induced endothelial cell apoptosis may be important in limiting endothelial cell proliferation after vascular injury.
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影响因子：
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作者：
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DOI：
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DOI：
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发表时间：
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期刊：
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影响因子：
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作者：
Rounds,S;Hsieh,L;Agarwal,KC
通讯作者：
Agarwal,KC