Distinct roles of arginases 1 and 2 in diabetic nephropathy.
Distinct roles of arginases 1 and 2 in diabetic nephropathy.
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精氨酸酶 1 和 2 在糖尿病肾病中的不同作用。
DOI：
10.1152/ajprenal.00158.2017
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发表时间：
2017
期刊：
影响因子：
--
通讯作者：
Awad,AlaaS
中科院分区：
文献类型：
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作者：
MorrisJr,SidneyM;You,Hanning;Gao,Ting;Vacher,Jean;Cooper,TimothyK;Awad,AlaaS
糖尿病是终末期肾脏疾病的主要原因，给受影响的个人造成了巨大的医疗负担和经济生产力损失。由于目前对糖尿病肾病进展的治疗只取得了一定的成功，识别疾病的潜在机制对于开发更有效的治疗方法是至关重要的。我们先前已经证明，使用精氨酸酶-(2-硼乙基)-L-半胱氨酸(BEC)的抑制或精氨酸酶-2同工酶的遗传缺陷对糖尿病小鼠模型肾病的关键特征具有保护作用。然而，这些研究并未确定是否所有的糖尿病肾病标志物仅依赖于精氨酸酶-2的表达。本研究的目的是找出与精氨酸酶-1或−-2表达特异相关的糖尿病肾病的特征。尿白蛋白排泄率和血浆尿素水平升高、肾纤维连接蛋白基因表达水平升高、肾髓质血流量减少几乎完全和特异地与精氨酸酶-2的表达有关，表明精氨酸酶-2选择性地介导了糖尿病肾损伤的主要方面。然而，肾巨噬细胞浸润和肾脏肿瘤坏死因子-α基因水平的增加不依赖于精氨酸酶-2的表达，但几乎完全被BEC处理所消除，表明精氨酸酶-1具有明显的作用。因此，我们建立了巨噬细胞特异性缺失精氨酸酶-1(CD11bCre/Arg1fl/fl)的小鼠。CD11bCre/Arg1fl/fl小鼠在链脲佐菌素诱导的糖尿病12周后，与Arg1fl/fl小鼠相比，巨噬细胞浸润显著减少，但对蛋白尿没有影响。这些结果表明，选择性抑制精氨酸酶-2将有效地预防或改善糖尿病肾损害的主要特征。
Diabetes is the leading cause of end-stage renal disease, resulting in a significant health care burden and loss of economic productivity by affected individuals. Because current therapies for progression of diabetic nephropathy (DN) are only moderately successful, identification of underlying mechanisms of disease is essential to develop more effective therapies. We showed previously that inhibition of arginase usingS-(2-boronoethyl)-l-cysteine (BEC) or genetic deficiency of the arginase-2 isozyme was protective against key features of nephropathy in diabetic mouse models. However, those studies did not determine whether all markers of DN were dependent only on arginase-2 expression. The objective of this study was to identify features of DN that are associated specifically with expression of arginase-1 or −2. Elevated urinary albumin excretion rate and plasma urea levels, increases in renal fibronectin mRNA levels, and decreased renal medullary blood flow were associated almost completely and specifically with arginase-2 expression, indicating that arginase-2 selectively mediates major aspects of diabetic renal injury. However, increases in renal macrophage infiltration and renal TNF-α mRNA levels occurred independent of arginase-2 expression but were almost entirely abolished by treatment with BEC, indicating a distinct role for arginase-1. We therefore generated mice with a macrophage-specific deletion of arginase-1 (CD11bCre/Arg1fl/fl).CD11bCre/Arg1fl/flmice had significantly reduced macrophage infiltration but had no effect on albuminuria compared withArg1fl/flmice after 12 wk of streptozotocin-induced diabetes. These results indicate that selective inhibition of arginase-2 would be effective in preventing or ameliorating major features of diabetic renal injury.
4 – 氢过氧化物和硫醇氧化剂在完整细胞和器官氧化应激研究中的应用
DOI：
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发表时间：
1985
期刊：
影响因子：
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作者：
H. Sies
通讯作者：
H. Sies
灌注大鼠肝脏中有机氢过氧化物还原、氨基比林去甲基化和某些物质氧化过程中观察到的谷胱甘肽释放特性及其对过氧化氢酶生理功能的影响。
DOI：
10.1042/bj1620509
发表时间：
1977
期刊：
The Biochemical journal
影响因子：
--
作者：
N. Oshino;B. Chance
通讯作者：
B. Chance