Mechanosensitive release of adenosine 5'-triphosphate through pannexin channels and mechanosensitive upregulation of pannexin channels in optic nerve head astrocytes: a mechanism for purinergic involvement in chronic strain.
Mechanosensitive release of adenosine 5'-triphosphate through pannexin channels and mechanosensitive upregulation of pannexin channels in optic nerve head astrocytes: a mechanism for purinergic involvement in chronic strain.
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DOI：
10.1002/glia.22695
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发表时间：
2014-09
期刊：
影响因子：
6.2
通讯作者：
Mitchell, Claire H.
中科院分区：
文献类型：
--
作者：
Beckel, Jonathan M.;Argall, Arthur J.;Lim, Jason C.;Xia, Jingsheng;Lu, Wennan;Coffey, Erin E.;Macarak, Edward J.;Shahidullah, Mohammed;Delamere, Nicholas A.;Zode, Gulab S.;Sheffield, Val C.;Shestopalov, Valery I.;Laties, Alan M.;Mitchell, Claire H.
由于从星形胶质细胞释放的ATP可以调节许多神经信号系统，因此这种ATP释放的触发和途径是重要的。在这里，机械应变触发ATP释放通过泛连接蛋白通道的能力，和持续应变对泛连接蛋白表达的影响，在大鼠视神经乳头星形胶质细胞进行了检查。星形胶质细胞释放ATP时，受到5%等双轴应变或低渗肿胀。虽然星形胶质细胞表达泛连接蛋白1-3、连接蛋白43和VNUT的mRNA，但药理学分析表明泛连接蛋白在机械敏感性ATP释放中起主导作用，Rho激酶起作用。来自panx 1 −/−小鼠的星形胶质细胞降低了基线水平，刺激了细胞外ATP的水平，证实了pannexins的作用。肿胀的星形胶质细胞触发了调节体积的减少，被腺苷三磷酸双磷酸酶或丙磺舒抑制。除了腺苷三磷酸双磷酸酶和羧苯氧乙烯酮外，P2 X7受体拮抗剂A438079和AZ 10606120还可抑制肿胀诱导的钙升高。体外星形胶质细胞延长牵张可上调panx 1和panx 2 mRNA的表达。在慢性青光眼的Tg-MYOCY 437 H小鼠模型的视神经头组织中观察到类似的体内上调; panx 1、panx 2和panx 3的基因增加，而免疫组织化学证实了泛连接蛋白1蛋白的表达增加。总之，星形胶质细胞释放ATP响应机械应变，泛连接蛋白1的主要流出途径。持续应变上调pannexins在体外和体内。这些发现共同提供了一种机制，通过这种机制，细胞外ATP在慢性机械应变下保持升高，如青光眼患者的视神经乳头中所发现的。
As ATP released from astrocytes can modulate many neural signaling systems, the triggers of and pathways for this ATP release are important. Here, the ability of mechanical strain to trigger ATP release through pannexin channels, and the effects of sustained strain on pannexin expression, were examined in rat optic nerve head astrocytes. Astrocytes released ATP when subjected to 5% equibiaxial strain or to hypotonic swelling. While astrocytes expressed mRNA for pannexins 1–3, connexin 43 and VNUT, pharmacological analysis suggested a predominant role for pannexins in mechanosensitive ATP release, with Rho kinases contributing. Astrocytes from panx1−/− mice had reduced baseline and stimulated levels of extracellular ATP, confirming the role for pannexins. Swelling astrocytes triggered a regulatory volume decrease that was inhibited by apyrase or probenecid. The swelling–induced rise in calcium was inhibited by P2X7 receptor antagonists A438079 and AZ10606120, in addition to apyrase and carbenoxelone. Extended stretch of astrocytes in vitro upregulated expression of panx1 and panx2 mRNA. A similar upregulation was observed in vivo in optic nerve head tissue from the Tg-MYOCY437H mouse model of chronic glaucoma; genes for panx1, panx2 and panx3 were increased while immunohistochemistry confirmed increased expression of pannexin 1 protein. In summary, astrocytes released ATP in response to mechanical strain, with pannexin 1 the predominant efflux pathway. Sustained strain upregulated pannexins in vitro and in vivo. Together these findings provide a mechanism by which extracellular ATP remains elevated under chronic mechanical strain, as found in the optic nerve head of patients with glaucoma.
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DOI：
10.1073/pnas.95.26.15735
发表时间：
1998-12-22
影响因子：
11.1
作者：
Cotrina, ML;Lin, JHC;Nedergaard, M
通讯作者：
Nedergaard, M
影响因子：
4.8
作者：
Coco, S;Calegari, F;Verderio, C
通讯作者：
Verderio, C
影响因子：
2.5
作者：
Darby, M;Kuzmiski, JB;MacVicar, BA
通讯作者：
MacVicar, BA
影响因子：
4.8
作者：
Guha, Sonia;Baltazar, Gabriel C.;Mitchell, Claire H.
通讯作者：
Mitchell, Claire H.
影响因子：
5.5
作者：
Dubyak, George R.
通讯作者：
Dubyak, George R.