Role of the intracellular nucleoside transporter ENT3 in transmitter and high K+ stimulation of astrocytic ATP release investigated using siRNA against ENT3.
Role of the intracellular nucleoside transporter ENT3 in transmitter and high K+ stimulation of astrocytic ATP release investigated using siRNA against ENT3.
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DOI：
10.1177/1759091414543439
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发表时间：
2014
期刊：
影响因子：
4.7
通讯作者：
Peng L
中科院分区：
文献类型：
--
作者：
Song D;Xu J;Bai Q;Cai L;Hertz L;Peng L
本研究探讨细胞内腺苷转运体平衡核苷转运体3(ENT3)在刺激星形胶质细胞释放神经胶质递质三磷酸腺苷(ATP)中的作用。在过去的20年里，我们对星形细胞处理腺苷的重要性、腺苷的磷酸化以及作为重要递质的星形细胞ATP的释放有了很大的了解。最近的一项研究表明，主要在细胞内的核苷转运蛋白ENT3在新分离的星形胶质细胞中的表达比在相应的神经元标本中要高得多，这表明ENT3在腺苷合成神经胶质递质ATP中起着重要作用。这与之前注意到的星形胶质细胞中ATP递质释放的延迟是一致的，但在神经元中不是。通过荧光素-荧光素酶反应，本研究证实并定量了谷氨酸、腺苷或高K+浓度对分化良好的星形胶质细胞的刺激释放。结果表明，无论受到何种刺激，下调ENT3和小干扰RNA(SiRNA)均可消除刺激后的ATP释放。成熟星形胶质细胞中的递质三磷酸腺苷是在释放之前直接由腺苷合成的，这一观点得到了星形胶质细胞囊泡转运体SLC17A9表达的出生后发展的支持。在神经元中，这种转运蛋白将ATP带入突触小泡，但在星形胶质细胞中，它只在未成熟细胞中表达，并在出生后3周内迅速下降，在分化良好的星形胶质细胞中，它在第三周末几乎消失，在那里它的作用可能已经被ENT3取代。
This study investigates the role of the intracellular adenosine transporter equilibrative nucleoside transporter 3 (ENT3) in stimulated release of the gliotransmitter adenosine triphosphate (ATP) from astrocytes. Within the past 20 years, our understanding of the importance of astrocytic handling of adenosine, its phosphorylation to ATP, and release of astrocytic ATP as an important transmitter has become greatly expanded. A recent demonstration that the mainly intracellular nucleoside transporter ENT3 shows much higher expression in freshly isolated astrocytes than in a corresponding neuronal preparation leads to the suggestion that it was important for the synthesis of gliotransmitter ATP from adenosine. This would be consistent with a previously noted delay in transmitter release of ATP in astrocytes but not in neurons. The present study has confirmed and quantitated stimulated ATP release in response to glutamate, adenosine, or an elevated K+ concentration from well-differentiated astrocyte cultures, measured by a luciferin–luciferase reaction. It showed that the stimulated ATP release was abolished by downregulation of ENT3 with small interfering RNA (siRNA), regardless of the stimulus. The concept that transmitter ATP in mature astrocytes is synthesized directly from adenosine prior to release is supported by the postnatal development of the expression of the vesicular transporter SLC17A9 in astrocytes. In neurons, this transporter carries ATP into synaptic vesicles, but in astrocytes, its expression is pronounced only in immature cells and shows a rapid decline during the first 3 postnatal weeks so that it has almost disappeared at the end of the third week in well-differentiated astrocytes, where its role has probably been taken over by ENT3.
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DOI：
10.1007/978-3-319-08894-5_3
发表时间：
2014-01-01
期刊：
GLUTAMATE AND ATP AT THE INTERFACE OF METABOLISM AND SIGNALING IN THE BRAIN
影响因子：
--
作者：
Hertz, Leif;Xu, Junnan;Peng, Liang
通讯作者：
Peng, Liang
影响因子：
1.4
作者：
Nakagawa, Takahiro;Otsuki, Naoki;Nibu, Ken-Ichi
通讯作者：
Nibu, Ken-Ichi
星形胶质细胞中糖原分解对吸收增加的细胞外 K 的要求：对脑中 K 稳态和糖原使用的潜在影响
影响因子：
4.4
作者：
Xu, Junnan;Song, Dan;Peng, Liang
通讯作者：
Peng, Liang
影响因子：
5.2
作者：
Peng L;Guo C;Wang T;Li B;Gu L;Wang Z
通讯作者：
Wang Z
影响因子：
4.8
作者：
Coco, S;Calegari, F;Verderio, C
通讯作者：
Verderio, C