ATP release from vascular endothelia occurs across Cx43 hemichannels and is attenuated during hypoxia.
ATP release from vascular endothelia occurs across Cx43 hemichannels and is attenuated during hypoxia.
复制标题
DOI：
10.1371/journal.pone.0002801
复制
发表时间：
2008-07-30
期刊：
影响因子：
3.7
通讯作者：
Eltzschig, Holger K.
中科院分区：
文献类型：
--
作者：
Faigle, Marion;Seessle, Jessica;Zug, Stephanie;El Kasmi, Karim C.;Eltzschig, Holger K.
细胞外ATP是血管适应有限氧可用性（缺氧）的重要信号分子。在这里，我们探讨了在缺氧条件下血管内皮对细胞外ATP释放的贡献。我们通过研究缺氧前内皮细胞（HMEC-1）的ATP释放获得了第一个见解。令人惊讶的是，我们发现缺氧暴露（2%氧气，48小时后22±3%）后ATP释放明显减弱。相反，细胞内ATP不变。同样，乳酸脱氢酶释放到上清液中在常氧和缺氧的内皮中相似，这表明在常氧和缺氧之间溶解ATP释放的差异很小。接下来，我们使用药理学策略来研究内皮依赖性ATP释放的潜在机制（例如维拉帕米、双嘧达莫、18- α -甘草次酸、阿南达胺、连接蛋白模拟肽）。这些研究表明，内皮细胞ATP释放发生-至少部分-通过连接蛋白43 （Cx43）半通道。内皮连接蛋白表达的实时RT-PCR显示Cx43转录物的选择性抑制，其他研究证实缺氧时Cx43 mRNA、总蛋白和表面蛋白的抑制具有时间依赖性。此外，缺氧导致Cx43-丝氨酸368磷酸化，已知这将Cx43半通道从开放状态切换到封闭状态。综上所述，这些研究暗示内皮细胞Cx43与缺氧相关的内皮细胞ATP释放抑制有关。
Extracellular ATP is an important signaling molecule for vascular adaptation to limited oxygen availability (hypoxia). Here, we pursued the contribution of vascular endothelia to extracellular ATP release under hypoxic conditions. We gained first insight from studying ATP release from endothelia (HMEC-1) pre-exposed to hypoxia. Surprisingly, we found that ATP release was significantly attenuated following hypoxia exposure (2% oxygen, 22±3% after 48 h). In contrast, intracellular ATP was unchanged. Similarly, lactate-dehydrogenase release into the supernatants was similar between normoxic or hypoxic endothelia, suggesting that differences in lytic ATP release between normoxia or hypoxia are minimal. Next, we used pharmacological strategies to study potential mechanisms for endothelial-dependent ATP release (eg, verapamil, dipyridamole, 18-alpha-glycyrrhetinic acid, anandamide, connexin-mimetic peptides). These studies revealed that endothelial ATP release occurs – at least in part - through connexin 43 (Cx43) hemichannels. A real-time RT-PCR screen of endothelial connexin expression showed selective repression of Cx43 transcript and additional studies confirmed time-dependent Cx43 mRNA, total and surface protein repression during hypoxia. In addition, hypoxia resulted in Cx43-serine368 phosphorylation, which is known to switch Cx43 hemi-channels from an open to a closed state. Taken together, these studies implicate endothelial Cx43 in hypoxia-associated repression of endothelial ATP release.
登录
查看更多内容
影响因子：
4.8
作者：
Gerasimovskaya, EV;Ahmad, S;Stenmark, KR
通讯作者：
Stenmark, KR
影响因子：
20.3
作者：
Eltzschig, HK;Thompson, LF;Colgan, SP
通讯作者：
Colgan, SP
影响因子：
37.8
作者：
Koehler, David;Eckle, Tobias;Eltzschig, Holger K.
通讯作者：
Eltzschig, Holger K.
影响因子：
6.5
作者：
ADES, EW;CANDAL, FJ;LAWLEY, TJ
通讯作者：
LAWLEY, TJ
影响因子：
20.3
作者：
Eckle, Tobias;Faigle, Marion;Eltzschig, Holger K.
通讯作者：
Eltzschig, Holger K.