Cellular adaptive changes in AKI: mitigating renal hypoxic injury
Cellular adaptive changes in AKI: mitigating renal hypoxic injury
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DOI：
10.1093/ndt/gfs100
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发表时间：
2012-05-01
影响因子：
6.1
通讯作者：
Rosenberger, Christian
中科院分区：
文献类型：
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作者：
Heyman, Samuel N.;Evans, Roger G.;Rosenberger, Christian
缺氧在缺血性、中毒性和脓毒症引起的急性肾损伤中起作用。不断发展的缺氧触发肾脏适应性反应，可能减轻损伤，导致亚致死形式的细胞损伤。肾脏下调用于肾小管运输的氧消耗的独特能力可以代表促进维持肾氧合的一种适应性反应，从而保持细胞完整性。Tran等人最近探索了一种新的机制，可能通过下调线粒体生物发生和氧消耗来预防肾小管损伤。利用内毒素血症啮齿动物肾脏RNA的表达谱以及体外和PGC-1 α基因敲除小鼠的补充研究，他们发现了与脓毒症相关的PPAR γ共激活因子-1 α（PGC-1 α）表达和参与氧化磷酸化的PGC-1 α依赖性基因的下降。这种反应可能解释了他们观察到的一个矛盾的保存肾氧合和结构完整性脓毒症，尽管减少肾血流量和氧气输送。因此，重置线粒体呼吸和氧消耗在败血症可能会被添加到不断增长的适应性反应，发生在缺氧应激。这篇综述将集中在这些机制，减轻不断发展的缺氧损伤，甚至在短暂的肾功能不全的代价。
Hypoxia plays a role in ischemic, toxic and sepsis-induced acute kidney injury. Evolving hypoxia triggers renal adaptive responses that may mitigate the insult, leading to sublethal forms of cell injury. The unique capability of the kidney to downregulate oxygen consumption for tubular transport could represent one such adaptive response which promotes maintenance of renal oxygenation, thereby preserving cellular integrity. Tran et al. recently explored a novel mechanism that might prevent tubular damage by downregulation of mitochondrial biogenesis and oxygen consumption. Using expression profiling of kidney RNA in endotoxemic rodents and complementary studies in vitro and in PGC-1 alpha knockout mice, they found a sepsis-related decline in PPAR gamma coactivator-1 alpha (PGC-1 alpha) expression and of PGC-1 alpha-dependent genes involved in oxidative phosphorylation. This response may explain their observation of a paradoxical preservation of kidney oxygenation and structural integrity in sepsis, despite reduced renal blood flow and oxygen delivery. Thus, resetting of mitochondrial respiration and oxygen consumption during sepsis might be added to the growing list of adaptive responses that occur during hypoxic stress. This review will focus on these mechanisms that mitigate evolving hypoxic injury, even at the expense of transient renal dysfunction.