Under acute hypoxia, multiple ion channels on the cell membrane are activated, causing cell swelling and eventually necrosis. LRRC8A is an indispensable protein of the volume-regulated anion channel (VRAC), which participates in swelling and the acceleration of cell necrosis. In this study, we revealed a dynamic change in the expression level of the LRRC8 family during hypoxia in 3T3-L1 cells. The disruption of LRRC8A in 3T3-L1 cells was also associated with a significant anti-necrotic phenotype upon hypoxia accompanied by the reduced expression of necrosis-related genes. In vivo, differential expression of LRRC8 family members was also identified between high-altitude pigs and their low-altitude relatives. Taken these findings together, this study demonstrates the involvement of LRRC8A in hypoxia-induced cell necrosis.

中文翻译：

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LRRC8A的缺乏减弱了3T3-L1细胞中缺氧诱导的坏死。

在急性缺氧状态下，细胞膜上的多个离子通道被激活，导致细胞肿胀并最终坏死。LRRC8A是体积调节阴离子通道（VRAC）不可或缺的蛋白质，它参与肿胀和细胞坏死的加速。在这项研究中，我们揭示了3T3-L1细胞缺氧期间LRRC8家族表达水平的动态变化。缺氧时，3T3-L1细胞中LRRC8A的破坏还与明显的抗坏死表型有关，同时伴有坏死相关基因的表达降低。在体内，还确定了高海拔猪及其低海拔亲戚之间LRRC8家族成员的差异表达。综合这些发现，本研究证明LRRC8A参与缺氧诱导的细胞坏死。