Poly (ADP-ribose) polymerase mediates diabetes-induced retinal neuropathy.
Poly (ADP-ribose) polymerase mediates diabetes-induced retinal neuropathy.
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DOI：
10.1155/2013/510451
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发表时间：
2013
影响因子：
4.6
通讯作者：
Abu El-Asrar AM
中科院分区：
文献类型：
--
作者：
Mohammad G;Siddiquei MM;Abu El-Asrar AM
视网膜神经病变是糖尿病视网膜病变发生的早期事件。糖尿病视网膜中被氧化应激激活的潜在酶之一是聚(ADP-核糖)聚合酶(PARP)。我们观察了PARP抑制剂1，5-异喹啉二醇对糖尿病大鼠视网膜神经退行性变介质和标志物表达的影响。链脲佐菌素诱导糖尿病大鼠2周后，给予1，5-异喹啉二醇(3 mg/kg/d)治疗。糖尿病4周后处死大鼠，荧光分光光度法检测视网膜组织中活性氧(ROS)含量，Western印迹法检测PARP、磷酸化ERK1/2、BDNF、突触素、谷氨酰胺合成酶(GS)和半胱氨酸天冬氨酸氨基转移酶(caspase-3)的表达。与非糖尿病大鼠相比，糖尿病大鼠视网膜ROS、PARP-1/2、磷酸化ERK1/2和裂解caspase-3的表达显著增加，而BDNF突触素和GS的表达显著降低。给予1，5-异喹啉二醇不影响糖尿病大鼠的代谢状态，但显著减轻糖尿病引起的PARP、ROS、ERK1/2磷酸化上调、caspase-3断裂以及BDNF、突触素和GS的下调。这些发现表明，PARP抑制剂在增加神经营养支持和改善糖尿病引起的早期视网膜神经病变方面具有有益的作用。
Retinal neuropathy is an early event in the development of diabetic retinopathy. One of the potential enzymes that are activated by oxidative stress in the diabetic retina is poly (ADP-ribose) polymerase (PARP). We investigated the effect of the PARP inhibitor 1,5-isoquinolinediol on the expression of the neurodegeneration mediators and markers in the retinas of diabetic rats. After two weeks of streptozotocin-induced diabetes, rats were treated with 1,5-isoquinolinediol (3 mg/kg/day). After 4 weeks of diabetes, the retinas were harvested and the levels of reactive oxygen species (ROS) were determined fluorometrically and the expressions of PARP, phosporylated-ERK1/2, BDNF, synaptophysin, glutamine synthetase (GS), and caspase-3 were determined by Western blot analysis. Retinal levels of ROS, PARP-1/2, phosphorylated ERK1/2, and cleaved caspase-3 were significantly increased, whereas the expressions of BDNF synaptophysin and GS were significantly decreased in the retinas of diabetic rats, compared to nondiabetic rats. Administration of 1,5-isoquinolinediol did not affect the metabolic status of the diabetic rats, but it significantly attenuated diabetes-induced upregulation of PARP, ROS, ERK1/2 phosphorylation, and cleaved caspase-3 and downregulation of BDNF, synaptophysin, and GS. These findings suggest a beneficial effect of the PARP inhibitor in increasing neurotrophic support and ameliorating early retinal neuropathy induced by diabetes.
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DOI：
10.1038/labinvest.2010.89
发表时间：
2010-09
期刊：
Laboratory investigation; a journal of technical methods and pathology
影响因子：
--
作者：
通讯作者：
--
影响因子：
7.7
作者：
Lieth, E;Barber, AJ;Strother, JM
通讯作者：
Strother, JM
影响因子：
4.4
作者：
Kowluru, Renu A.;Menon, Bindu;Gierhart, Dennis L.
通讯作者：
Gierhart, Dennis L.
影响因子：
2.9
作者：
Nag, TC;Wadhwa, S
通讯作者：
Wadhwa, S
影响因子：
5.6
作者：
Ola MS;Nawaz MI;Khan HA;Alhomida AS
通讯作者：
Alhomida AS