Long-lived lens fiber cells require a robust cellular protective function against oxidative insults to maintain their hemostasis and viability; however, the underlying mechanism is largely obscure. In this study, we unveiled a new mechanism that protects lens fiber cells against oxidative stress-induced cell death. We found that mechano-activated connexin (Cx) hemichannels (HCs) mediate the transport of glutathione (GSH) into chick embryonic fibroblasts (CEF) and primary lens fiber cells, resulting in a decrease in the accumulation of intracellular reactive oxygen species induced by both HO and ultraviolet B, providing protection to lens fiber cells against cell apoptosis and necrosis. Furthermore, HCs formed by both homomeric Cx50 or Cx46 and heteromeric Cx50/Cx46 were mechanosensitive and could transport GSH into CEF cells. Notably, mechano-activated Cx50 HCs exhibited a greater capacity to transport GSH than Cx46 HCs. Consistently, the deficiency of Cx50 in single lens fiber cells led to a higher level of oxidative stress. Additionally, outer cortical short lens fiber cells expressing full length Cxs demonstrated greater resistance to oxidative injury compared to central core long lens fibers. Taken together, our results suggest that the activation of Cx HCs by interstitial fluid flow in cultured epithelial cells and isolated fiber cells shows that HCs can serve as a pathway for moving GSH across the cell membrane to offer protection against oxidative stress.

中文翻译：

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机械激活的连接蛋白半通道和谷胱甘肽运输保护晶状体纤维细胞免受氧化损伤


长寿命的晶状体纤维细胞需要强大的细胞保护功能来抵抗氧化损伤，以维持其止血和活力；然而，其基本机制在很大程度上尚不清楚。在这项研究中，我们揭示了一种保护晶状体纤维细胞免受氧化应激诱导的细胞死亡的新机制。我们发现机械激活的连接蛋白 (Cx) 半通道 (HC) 介导谷胱甘肽 (GSH) 转运至鸡胚胎成纤维细胞 (CEF) 和初级晶状体纤维细胞中，从而导致细胞内活性氧的积累减少。 H2O 和紫外线 B，为晶状体纤维细胞提供保护，防止细胞凋亡和坏死。此外，由同聚体 Cx50 或 Cx46 和异聚体 Cx50/Cx46 形成的 HC 具有机械敏感性，并且可以将 GSH 转运到 CEF 细胞中。值得注意的是，机械激活的 Cx50 HC 比 Cx46 HC 表现出更强的 GSH 运输能力。一致地，单晶状体纤维细胞中 Cx50 的缺乏导致更高水平的氧化应激。此外，与中央核心长晶状体纤维相比，表达全长 Cxs 的外皮层短晶状体纤维细胞表现出更强的抗氧化损伤能力。综上所述，我们的结果表明，培养的上皮细胞和分离的纤维细胞中的间质液流对 Cx HC 的激活表明，HC 可以作为 GSH 穿过细胞膜的途径，从而提供针对氧化应激的保护。