PDF(Pubmed)
Abstract：
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 H2O2 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.
摘要：
长寿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，潜在的机制在很大程度上是模糊的。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（HCs）介导谷胱甘肽（GSH）向雏鸡胚胎成纤维细胞（CEF）和原代晶状体纤维细胞的转运，导致H2O2和紫外线B诱导的细胞内活性氧的积累减少，保护晶状体纤维细胞免受细胞凋亡和坏死。此外，同型Cx50或Cx46和异型Cx50/Cx46形成的HC对机械敏感，可以将GSH转运到CEF细胞中。值得注意的是,机械活化的Cx50HCs比Cx46HCs具有更大的GSH转运能力。始终如一，单晶状体纤维细胞中Cx50的缺乏导致较高水平的氧化应激。此外,与中央核心长晶状体纤维相比，表达全长Cxs的外皮质短晶状体纤维细胞对氧化损伤具有更大的抵抗力。一起来看,我们的结果表明,培养的上皮细胞和分离的成纤维细胞中的间质液流动对CxHCs的激活表明,HCs可以作为GSH穿过细胞膜的途径,从而提供抗氧化应激的保护.
