Yang Di, Chen Mengyuan, Yang Sijia, Deng Furong, Guo Xinbiao
Department of Occupational and Environmental Health Sciences, School of Public Health, Peking University, No. 38 Xueyuan Road, Beijing, China.
Department of Occupational and Environmental Health Sciences, School of Public Health, Peking University, No. 38 Xueyuan Road, Beijing, China.
Toxicology. 2023 Apr;488:153488. doi: 10.1016/j.tox.2023.153488. Epub 2023 Mar 12.
Connexin hemichannels and pannexin channels are two types of transmembrane channels that allow autocrine/paracrine signalling through the exchange of ions and molecules between the intra- and extracellular compartments. However, owing to the poor selectivity of permeable ions and metabolites, the massive opening of these plasma membrane channels can lead to an excessive influx of toxic substances and an outflux of essential metabolites, such as adenosine triphosphate, glutathione, glutamate and ions, resulting in unbalanced cell homeostasis and impaired cell function. It is becoming increasingly clear that these channels can be activated in response to external stimuli and are involved in toxicity, yet their concrete mechanistic roles in the toxic effects induced by stress and various environmental changes remain poorly defined. This review provides an updated understanding of connexin hemichannels and pannexin channels in response to multiple extrinsic stressors and how these activated channels and their permeable messengers participate in toxicological pathways and processes, including inflammation, oxidative damage, intracellular calcium imbalance, bystander DNA damage and excitotoxicity.
连接蛋白半通道和泛连接蛋白通道是两种跨膜通道，它们通过细胞内和细胞外区室之间的离子和分子交换实现自分泌/旁分泌信号传导。然而，由于可渗透离子和代谢物的选择性较差，这些质膜通道的大量开放会导致有毒物质的过度内流以及三磷酸腺苷、谷胱甘肽、谷氨酸和离子等必需代谢物的外流，从而导致细胞内稳态失衡和细胞功能受损。越来越清楚的是，这些通道可响应外部刺激而被激活并参与毒性作用，然而它们在应激和各种环境变化诱导的毒性效应中的具体机制作用仍不清楚。本综述提供了关于连接蛋白半通道和泛连接蛋白通道对多种外在应激源的反应的最新认识，以及这些激活的通道及其可渗透信使如何参与毒理学途径和过程，包括炎症、氧化损伤、细胞内钙失衡、旁观者DNA损伤和兴奋性毒性。
