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Gyroxin, a toxin from Crotalus durissus terrificus snake venom, induces a calcium dependent increase in glutamate release in mice brain cortical synaptosomes
Neuropeptides ( IF 2.5 ) Pub Date : 2020-10-01 , DOI: 10.1016/j.npep.2020.102081
C Z Ferrari 1 , R Ribeiro 1 , A M Lima 2 , A M Soares 3 , W L G Cavalcante 1 , L B Vieira 1
Affiliation  

Gyroxin is a thrombin-like toxin obtained from the venom of the South American rattlesnake, Crotalus durissus terrificus. Literature has reported "gyroxin syndrome" characterized, in mice, as series of aberrant motor behavior, known as barrel rotation, mainly after intraperitoneal administration. Despites several studies, a physiological mechanism of "gyroxin syndrome" are still not completely understood. In this context, alterations on the central nervous system (CNS), especially causing neurotoxic events, are pointed out as likely candidates. Then, we decided to investigate whether gyroxin induces alterations in glutamate release, one of the most important neurotransmitter involved in neurotoxicity. For that, we performed all experiments, in vitro, using a model of mice brain cortical synaptosomes. Notably, our results indicate that the administration of gyroxin on purified presynaptic brain cortical terminals resulted in an extracellular Ca2+- dependent raise in glutamate release. Indeed, our results also showed that gyroxin increases intrasynaptosomal calcium (Ca2+) levels through acting on voltage gated calcium channels (VGCC), specifically N and P/Q subtypes. Moreover, our data show that gyroxin increases exocytosis rate. Interestingly, these data suggest that gyroxin might induce neurotoxicity by increasing glutamate levels. However, future investigations are needed in order to elucidate the nature of the following events.

中文翻译:

Gyroxin,一种来自 Crotalus durissus terrificus 蛇毒的毒素,诱导小鼠大脑皮质突触体中谷氨酸释放的钙依赖性增加

Gyroxin 是一种类似凝血酶的毒素,从南美响尾蛇 Crotalus durissus terrificus 的毒液中提取。文献报道了“gyroxin 综合征”,其特征在于小鼠的一系列异常运动行为,称为桶旋转,主要在腹腔给药后。尽管进行了多项研究,但仍未完全了解“gyroxin 综合征”的生理机制。在这种情况下,中枢神经系统 (CNS) 的改变,特别是引起神经毒性事件,被指出是可能的候选者。然后,我们决定研究 gyroxin 是否诱导谷氨酸释放的改变,谷氨酸释放是与神经毒性有关的最重要的神经递质之一。为此,我们使用小鼠大脑皮质突触体模型在体外进行了所有实验。尤其,我们的结果表明,在纯化的突触前大脑皮层末端施用 gyroxin 导致谷氨酸释放的细胞外 Ca2+ 依赖性升高。事实上,我们的结果还表明,gyroxin 通过作用于电压门控钙通道 (VGCC),特别是 N 和 P/Q 亚型,增加了突触体内钙 (Ca2+) 水平。此外,我们的数据显示 gyroxin 增加胞吐率。有趣的是,这些数据表明 gyroxin 可能通过增加谷氨酸水平来诱导神经毒性。但是,需要进一步调查以阐明以下事件的性质。我们的结果还表明,gyroxin 通过作用于电压门控钙通道 (VGCC),特别是 N 和 P/Q 亚型,增加了突触内钙 (Ca2+) 水平。此外,我们的数据显示 gyroxin 增加胞吐率。有趣的是,这些数据表明 gyroxin 可能通过增加谷氨酸水平来诱导神经毒性。但是,需要进一步调查以阐明以下事件的性质。我们的结果还表明,gyroxin 通过作用于电压门控钙通道 (VGCC),特别是 N 和 P/Q 亚型,增加了突触内钙 (Ca2+) 水平。此外,我们的数据显示 gyroxin 增加胞吐率。有趣的是,这些数据表明 gyroxin 可能通过增加谷氨酸水平来诱导神经毒性。但是,需要进一步调查以阐明以下事件的性质。
更新日期:2020-10-01
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