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首页> 外文期刊>Journal of cellular physiology. >L‐OPA1 deficiency aggravates necroptosis of alveolar epithelial cells through impairing mitochondrial function during acute lung injury in mice
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L‐OPA1 deficiency aggravates necroptosis of alveolar epithelial cells through impairing mitochondrial function during acute lung injury in mice

机译:L OPA1缺乏加剧necroptosis等通过损害肺泡上皮细胞在急性肺损伤的线粒体功能在老鼠身上

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Abstract Necroptosis, a recently described form of programmed cell death, is the main way of alveolar epithelial cells (AECs) death in acute lung injury (ALI). While the mechanism of how to trigger necroptosis in AECs during ALI has been rarely evaluated. Long optic atrophy protein 1 (L‐OPA1)?is a crucial mitochondrial inner membrane fusion protein, and its deficiency impairs mitochondrial function. This study aimed to investigate the role of L‐OPA1?deficiency‐mediated mitochondrial dysfunction in AECs necroptosis. We comprehensively investigated the detailed contribution and molecular mechanism of L‐OPA1?deficiency in AECs necroptosis by inhibiting or activating L‐OPA1.?First, our data showed that L‐OPA1 expression was downregulated in the lungs and AECs under the lipopolysaccharide (LPS) challenge. Furthermore, inhibition of L‐OPA1?aggravated the pathological injury, inflammatory response, and necroptosis in the lungs of LPS‐induced ALI mice. In vitro, inhibition of L‐OPA1?induced necroptosis of AECs, while activation of L‐OPA1?alleviated necroptosis of AECs under the LPS challenge. Mechanistically, inhibition of L‐OPA1?aggravated necroptosis of AECs by inducing mitochondrial fragmentation and reducing mitochondrial membrane potential. While activation of L‐OPA1?had the opposite effects. In summary, these findings indicate for the first time that L‐OPA1?deficiency mediates mitochondrial fragmentation, induces necroptosis of AECs, and exacerbates ALI in mice.
机译:抽象的Necroptosis,最近的描述形式程序性细胞死亡的主要方式肺泡上皮细胞(aec)在急性死亡肺损伤(ALI)。触发necroptosis原子能委员会在阿里很少进行评估。(L OPA1应承担的)?膜融合蛋白,其不足之处损害线粒体功能。调查的作用L OPA1应承担的吗?功能障碍在原子能委员会necroptosis。全面调查的详细贡献和分子机制L OPA1应承担的吗?抑制或激活OPA1。?表明,L OPA1表达下调在肺部和原子能委员会脂多糖(LPS)的挑战。抑制L OPA1应承担的吗?损伤、炎症反应和necroptosisLPS诱导ALI应承担的小鼠的肺。抑制L OPA1应承担的吗?而激活L OPA1应承担的?有限合伙人下原子能委员会的挑战。抑制L OPA1应承担的吗?诱导线粒体分裂和原子能委员会降低线粒体膜电位。L必经OPA1激活?总结,这些发现表明第一L OPA1应承担的时间吗?线粒体分裂,诱导necroptosis原子能委员会,加剧了阿里在老鼠身上。

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