Endothelin-1 protects astrocytes from hypoxic/ischemic injury
Endothelin-1 protects astrocytes from hypoxic/ischemic injury
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DOI：
10.1096/fj.99-1022com
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发表时间：
2001-03-01
期刊：
影响因子：
4.8
通讯作者：
Chung, SK
中科院分区：
文献类型：
--
作者：
Ho, MCY;Lo, ACY;Chung, SK
在病理条件下，如局部缺血（I）、蛛网膜下腔出血和阿尔茨海默病，星形胶质细胞显示内皮素（ET）样免疫反应性大幅增加。然而，目前尚不清楚ET在脑损伤期间对这些细胞是保护性的还是破坏性的。使用来自ET-1缺陷小鼠的星形胶质细胞，我们确定了在正常、缺氧（H）和缺氧/缺血（H/I）条件下ET-1对这些细胞的影响。在正常培养条件下，野生型和ET-1缺陷小鼠的星形胶质细胞在形态和细胞增殖率方面没有差异。ET-1缺陷的星形胶质细胞中ET-3和ETA受体mRNA表达上调，而ETB受体mRNA表达下调，表明ET-1和ET-3可能相互补充功能，这些内皮素及其受体的表达受复杂的反馈机制调节。在H和H/I条件下，野生型星形胶质细胞中ET-1肽和mRNA上调，并且没有ET-1的星形胶质细胞比野生型星形胶质细胞死亡更快，如更大的乳酸脱氢酶流出所示。本研究表明，没有ET-1的星形胶质细胞更容易受到H和H/I损伤，并且星形胶质细胞ET-1的上调对于星形胶质细胞的存活至关重要。何，M。C.是的，Lo，A. C.是的，栗原，H.，Yu，中国茶条A. C. H、钟，S。S. M.，钟，S。K.内皮素-1保护星形胶质细胞免受缺氧/缺血损伤。
Under pathological conditions such as ischemia (I), subarachnoid hemorrhage, and Alzheimer's disease, astrocytes show a large increase in endothelin (ET) -like immunoreactivity. However, it is not clear whether ET is protective or destructive to these cells during brain injury. Using astrocytes from ET-1-deficient mice, we determined the effect of ET-1 on these cells under normal, hypoxic (H), and hypoxic/ ischemic (H/I) conditions. Under normal culture conditions, astrocytes from wild-type and ET-l-deficient mice showed no difference in their morphology and cell proliferation rates. ET-3 and ETA receptor mRNAs were up-regulated whereas ETB receptor mRNA was down-regulated in ET-1-deficient astrocytes, suggesting that ET-1 and ET-3 may complement each other's functions and that the expressions of these endothelins and their receptors are regulated by a complex feedback mechanism. Under H and H/I conditions, ET-1 peptide and mRNA were up-regulated in wild-type astrocytes, and the astrocytes without ET-1 died faster than the wild-type astrocytes, as indicated by greater efflux of lactate dehydrogenase, The present study suggests that astrocytes without ET-1 are more vulnerable to H and H/I injuries and that the up-regulation of astrocytic ET-1 is essential for the survival of astrocytes.-Ho, M. C. Y., Lo, A. C. Y., Kurihara, H., Yu, A. C. H., Chung, S. S. M., Chung, S. K. Endothelin-1 protects astrocytes from hypoxic/ischemic injury.