Phospho-Site-Specific Antibody Microarray to Study the State of Protein Phosphorylation in the Retina.
Phospho-Site-Specific Antibody Microarray to Study the State of Protein Phosphorylation in the Retina.
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DOI：
10.4172/jpb.1000031
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发表时间：
2008-08-13
期刊：
影响因子：
--
通讯作者：
Rajala RV
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作者：
Rajala RV
神经退行性变是糖尿病视网膜病变的重要组成部分，在实验和人类糖尿病期间视网膜神经细胞凋亡增加。在糖尿病动物的整个视网膜中，山梨糖醇和果糖的积累以及氧化应激的产生或增强已被报道。醛糖还原酶（AR）是该途径中的第一种限速酶，可将葡萄糖还原为山梨醇，抑制AR的药物可预防糖尿病并发症。在本研究中，我们通过磷酸化位点特异性抗体微阵列检测了各种视网膜蛋白在山梨醇处理下的磷酸化状态。我们的研究结果表明，各种视网膜蛋白激酶和细胞骨架蛋白在山梨醇治疗下被激活或下调。此外，我们的研究还表明视网膜胰岛素和胰岛素生长因子1受体及其下游信号蛋白如磷酸肌苷3-激酶和蛋白激酶B （Akt）的激活。了解多元醇（山梨醇）通路中视网膜蛋白的调控，有助于设计治疗糖尿病视网膜病变的药物。
Neurodegeneration is an important component of diabetic retinopathy as demonstrated by increased neural apoptosis in the retina during experimental and human diabetes. Accumulation of sorbitol and fructose and the generation or enhancement of oxidative stress has been reported in the whole retina of diabetic animals. Aldose reductase (AR), the first and the rate limiting enzyme in the pathway reduces glucose to sorbitol and the diabetic complications are prevented by drugs that inhibit AR. In this study we examined the phosphorylation state of various retinal proteins in response to sorbitol-treatment by phosphor-site-specific antibody microarray. Our results suggest that various retinal protein kinases and cytoskeletal proteins either activated or down regulated in response to sorbitol treatment. Further, our study also indicates the activation of retinal insulin- and insulin growth factor 1 receptor and their downstream signaling proteins such as phosphoinositide 3-kinanse and protein kinase B (Akt). Understanding the regulation of retinal proteins involved in polyol (sorbitol) pathway would help to design therapeutic agents for the treatment of diabetic retinopathy.