Altered sphingomyelinase and ceramide expression in the setting of ischemic and nephrotoxic acute renal failure.
Altered sphingomyelinase and ceramide expression in the setting of ischemic and nephrotoxic acute renal failure.
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在缺血性和肾毒性急性肾衰竭的情况下改变鞘磷脂酶和神经酰胺的表达。
DOI：
10.1046/j.1523-1755.1998.00772.x
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发表时间：
1998
期刊：
影响因子：
--
通讯作者：
Burkhart,KM
中科院分区：
文献类型：
--
作者：
Zager,RA;Conrad,S;Lochhead,K;Sweeney,EA;Igarashi,Y;Burkhart,KM
缺血性和肾毒性急性肾功能衰竭时鞘磷脂酶和神经酰胺表达的改变多种物理和化学刺激可激活鞘磷脂酶（SMases），导致鞘磷脂（SM）水解并释放神经酰胺。由于神经酰胺可以深刻地影响宿主的稳态机制，因此出现了“SM（或SMase）信号通路”的概念。我们最近发现，在肾缺血时神经酰胺水平突然下降，然后在早期再灌注（30至90分钟）时反弹至正常值的两倍。因此，本研究评估了这些神经酰胺变化是否是可预测的，因此可能由SMase活性的可比变化介导。使小鼠经历45分钟的肾缺血± 30分钟、90分钟或24小时的再灌注。然后测定肾皮质（或分离的近端小管）的SMase活性（酸性、中性形式）。为了表征早期缺血后神经酰胺增量是否是相对持久的事件，在24小时再灌注期后测定神经酰胺。最后，为了评估观察到的扰动是否是缺血后损伤所特有的，在甘油诱导的肌血红蛋白尿和抗肾小球基底膜（αGBM）抗体诱导的急性肾衰竭（ARF）的情况下定量测定了SMase和神经酰胺。缺血诱导酸性和中性SMase活性突然下降（约50%），这些持续在整个24小时的再灌注的不懈的方式。然而，神经酰胺表达增加（2×正常）。肌血红蛋白尿症也抑制酸性/中性SMases，并再次观察到“矛盾”的神经酰胺增量。最后，αGBM肾炎增加神经酰胺水平，但在这种情况下，相关性是SMase活性增加。这些结果表明：（1）神经酰胺是一种急性肾“应激反应物”，对不同的肾损伤反应增加;（2）这种反应可能独立于经典SM途径发生，因为神经酰胺的增加似乎与SMase活性的增加无关;和（3）考虑到神经酰胺和SM（ase）途径对凋亡、细胞增殖、分化和组织炎症的充分记录的影响，本研究结果对不同形式ARF的诱导和演变具有潜在的广泛意义。
Altered sphingomyelinase and ceramide expression in the setting of ischemic and nephrotoxic acute renal failure.Diverse physical and chemical stimuli can activate sphingomyelinases (SMases), resulting in sphingomyelin (SM) hydrolysis with ceramide release. Since ceramide can profoundly impact a host of homeostatic mechanisms, the concept of a “SM (or SMase) signaling pathway” has emerged. We recently documented that ceramide levels fall abruptly during renal ischemia, and then rebound to twice normal values during early reperfusion (30 to 90 min). Therefore, the present study assessed whether these ceramide changes are paralleled, and hence potentially mediated, by comparable changes in SMase activity. Mice were subjected to 45 minutes of renal ischemia ± 30 minutes, 90 minutes, or 24 hours of reperfusion. Renal cortices (or isolated proximal tubules) were then assayed for SMase activity (acidic, neutral forms). To characterize whether early post-ischemic ceramide increments are a relatively persistent event, ceramide was assayed following a 24-hour reperfusion period. Finally, to assess whether the observed perturbations were unique to post-ischemic injury, SMase and ceramide were quantified in the setting of glycerol-induced myohemoglobinuria and anti-glomerular basement membrane (αGBM) antibody-induced acute renal failure (ARF). Ischemia induced abrupt declines (∼50%) in both acidic and neutral SMase activities, and these persisted in an unremitting fashion throughout 24 hours of reperfusion. Nevertheless, increased ceramide expression (2× normal) resulted. Myohemoglobinuria also suppressed acidic/neutral SMases, and again, “paradoxical” ceramide increments were observed. Finally,αGBM nephritis increased ceramide levels, but in this instance, a correlate was increased SMase activity. These results suggest that: (1) ceramide is an acute renal “stress reactant,” increasing in response to diverse renal insults; (2) this response may occur independently of the classic SM pathway, since the ceramide increments can seemingly be dissociated from increased SMase activity; and (3) given the well documented impact of ceramide and the SM(ase) pathway on apoptosis, cell proliferation, differentiation, and tissue inflammation, the present results have potentially broad ranging implications for the induction and evolution of diverse forms of ARF.
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DOI：
--
发表时间：
1992
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Younes,A;Kahn,DW;Besterman,JM;Bittman,R;Byun,HS;Kolesnick,RN
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Kolesnick,RN
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4.8
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19.6
作者：
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影响因子：
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通讯作者：
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