Regulation of Mct1 by cAMP-dependent internalization in rat brain endothelial cells.
Regulation of Mct1 by cAMP-dependent internalization in rat brain endothelial cells.
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DOI：
10.1016/j.brainres.2012.08.026
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发表时间：
2012-10-22
期刊：
影响因子：
2.9
通讯作者：
Drewes LR
中科院分区：
文献类型：
--
作者：
Smith JP;Uhernik AL;Li L;Liu Z;Drewes LR
在脑血管内皮中，单羧酸转运蛋白1（Mct 1）控制短链单羧酸和酮酸（包括丙酮酸和乳酸）的血脑转运，以支持脑能量代谢。在大鼠脑血管内皮细胞中，通过环磷酸腺苷（cAMP）的β-肾上腺素能信号传导，Mct 1功能急剧下降;然而，这种运输能力急性下降的机制尚不清楚。在这份报告中，我们证明，cAMP诱导脱磷酸化和内化Mct 1从质膜到小窝和早期内体在RBE 4大鼠脑血管内皮细胞系。此外，我们提供的证据表明，Mct 1组成型周期通过网格蛋白囊泡和回收内体的途径，这是不依赖于cAMP信号在这些细胞。我们的研究结果很重要，因为它们首次显示了脑血管内皮细胞中Mct 1的调节和不调节的囊泡运输;这些过程对于更好地理解正常脑能量代谢，以及治疗脑疾病（如脑卒中）的病因学和潜在治疗方法具有重要意义，其中乳酸酸中毒是关键组成部分
In the cerebrovascular endothelium, monocarboxylic acid transporter 1 (Mct1) controls blood-brain transport of short chain monocarboxylic and keto acids, including pyruvate and lactate, to support brain energy metabolism. Mct1 function is acutely decreased in rat brain cerebrovascular endothelial cells by β-adrenergic signaling through cyclic adenosine monophosphate (cAMP); however, the mechanism for this acute reduction in transport capacity is unknown. In this report, we demonstrate that cAMP induces the dephosphorylation and internalization of Mct1 from the plasma membrane into caveolae and early endosomes in the RBE4 rat brain cerebrovascular endothelial cell line. Additionally, we provide evidence that Mct1 constitutively cycles through clathrin vesicles and recycling endosomes in a pathway that is not dependent upon cAMP signaling in these cells. Our results are important because they show for the first time the regulated and unregulated vesicular trafficking of Mct1 in cerebrovascular endothelial cells; processes which have significance for better understanding normal brain energy metabolism, and the etiology and potential therapeutic approaches to treating brain diseases, such as stroke, in which lactic acidosis is a key component
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DOI：
10.1111/j.1600-0854.2010.01155.x
发表时间：
2011-04
期刊：
Traffic (Copenhagen, Denmark)
影响因子：
--
作者：
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通讯作者：
Philp NJ
DOI：
10.1152/ajpendo.1997.273.1.e207
发表时间：
1997-07-01
影响因子：
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作者：
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通讯作者：
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影响因子：
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影响因子：
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