Hyperglycemia induced damage to mitochondrial respiration in renal mesangial and tubular cells: Implications for diabetic nephropathy.
Hyperglycemia induced damage to mitochondrial respiration in renal mesangial and tubular cells: Implications for diabetic nephropathy.
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DOI：
10.1016/j.redox.2016.09.007
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发表时间：
2016-12
期刊：
影响因子：
11.4
通讯作者：
Malik, Afshan N.
中科院分区：
文献类型：
--
作者：
Czajka, Anna;Malik, Afshan N.
肾小管和系膜细胞的损伤是糖尿病肾病（DN）发展的核心，DN是糖尿病的并发症，可导致肾衰竭。线粒体是细胞呼吸的场所，并通过氧化磷酸化以ATP的形式产生能量，线粒体功能障碍与DN有关。由于肾脏是一个具有高生物能量需求的器官，我们假设高血糖会导致肾脏线粒体损伤，导致生物能量不足。利用海马生物分析仪比较了正常血糖和高血糖条件下人原代系膜细胞（HMCs）和近端肾小管细胞（HK-2）的生物能谱以及高血糖对细胞呼吸的影响。在正常情况下，HK-2有显着较低的基础，ATP相关的和最大的呼吸率，并降低储备能力相比，HMCs。在HK-2中，高血压在4天内引起所有呼吸参数的下调，但在HMCs中没有。高血糖8天后，肾小管细胞中呼吸参数持续下调，糖酵解代偿性上调。HMCs在第8天降低了最大呼吸和储备能力，到第12天损害了线粒体呼吸，尽管它们没有增强糖酵解。这些数据表明，糖尿病可能导致两种细胞类型中ATP产生的细胞缺陷，尽管具有不同的敏感性，并且这种机制可能显著导致糖尿病肾脏中观察到的细胞损伤。预防糖尿病引起的肾脏线粒体呼吸损伤可能是预防/治疗DN的一种新的治疗方法。肾脏作为一个器官有很高的生物能量需求。培养的肾小球系膜细胞和肾小管细胞具有不同的生物能谱。高血压对肾细胞线粒体代谢有毒性作用。肾小球系膜细胞比肾小管细胞更能抵抗糖尿病引起的细胞呼吸损伤。肾细胞能量缺乏可能是糖尿病肾病肾损害的一个促成因素。
Damage to renal tubular and mesangial cells is central to the development of diabetic nephropathy (DN), a complication of diabetes which can lead to renal failure. Mitochondria are the site of cellular respiration and produce energy in the form of ATP via oxidative phosphorylation, and mitochondrial dysfunction has been implicated in DN. Since the kidney is an organ with high bioenergetic needs, we postulated that hyperglycemia causes damage to renal mitochondria resulting in bioenergetic deficit. The bioenergetic profiles and the effect of hyperglycemia on cellular respiration of human primary mesangial (HMCs) and proximal tubular cells (HK-2) were compared in normoglycemic and hyperglycemic conditions using the seahorse bio-analyzer. In normoglycemia, HK-2 had significantly lower basal, ATP-linked and maximal respiration rates, and lower reserve capacity compared to HMCs. Hyperglycemia caused a down-regulation of all respiratory parameters within 4 days in HK-2 but not in HMCs. After 8 days of hyperglycemia, down-regulation of respiratory parameters persisted in tubular cells with compensatory up-regulated glycolysis. HMCs had reduced maximal respiration and reserve capacity at 8 days, and by 12 days had compromised mitochondrial respiration despite which they did not enhance glycolysis. These data suggest that diabetes is likely to lead to a cellular deficit in ATP production in both cell types, although with different sensitivities, and this mechanism could significantly contribute to the cellular damage seen in the diabetic kidney. Prevention of diabetes induced damage to renal mitochondrial respiration may be a novel therapeutic approach for the prevention/treatment of DN. The kidney as an organ has high bioenergetic needs. Cultured renal mesangial and tubular cells have different bioenergetic profiles. Hyperglycemia had a toxic effect on renal cell mitochondrial metabolism. Mesangial cells were more resistant to diabetes induced damage to cellular respiration than tubular cells. Energy deficit in renal cells may be a contributing factor to renal damage in diabetic nephropathy.
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作者：
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通讯作者：
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DOI：
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