Rajala Raju V S
Departments of Ophthalmology and Cell Biology, and Dean A. McGee Eye Institute, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
J Proteomics Bioinform. 2008 Aug 13;1:242. doi: 10.4172/jpb.1000031.
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.
神经退行性变是糖尿病视网膜病变的一个重要组成部分，实验性糖尿病和人类糖尿病患者视网膜中神经细胞凋亡增加就证明了这一点。在糖尿病动物的整个视网膜中，已报道山梨醇和果糖的积累以及氧化应激的产生或增强。醛糖还原酶（AR）是该途径中的第一个限速酶，它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山梨醇处理后各种视网膜蛋白的磷酸化状态。我们的结果表明，各种视网膜蛋白激酶和细胞骨架蛋白在山梨醇处理后被激活或下调。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醇3激酶和蛋白激酶B（Akt）被激活。了解参与多元醇（山梨醇）途径的视网膜蛋白的调节将有助于设计治疗糖尿病视网膜病变的治疗药物。
