Characterization of the vitreous proteome in diabetes without diabetic retinopathy and diabetes with proliferative diabetic retinopathy

Characterization of the vitreous proteome in diabetes without diabetic retinopathy and diabetes with proliferative diabetic retinopathy
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DOI:
10.1021/pr800112g
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发表时间:
2008-06-01
影响因子:
4.4
通讯作者:
Feener, Edward P.
Feener, Edward P.
中科院分区:
生物学2区
文献类型:
--
作者:
Gao, Ben-Bo;Chen, Xiaohong;Feener, Edward P.

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在没有和存在增殖性糖尿病视网膜病变(PDR)的情况下,了解糖尿病诱导的玻璃体蛋白组成的改变可能为了解这种疾病的因素和机制提供见解。我们对糖尿病但无糖尿病视网膜病变(noDR)或PDR和非糖尿病个体(NDM)的玻璃体样本进行了全面的蛋白质组学分析和比较。利用17个独立玻璃体样品的单维sds - page和纳米lc /MS/MS技术,鉴定了252个玻璃体蛋白。与NDM玻璃体相比,noDR和PDR玻璃体中56种蛋白差异丰富,其中PDR玻璃体中32种蛋白较NDM玻璃体增加,10种蛋白较NDM玻璃体减少。比较noDR组和PDR组,PDR玻璃体中血管紧张素原水平升高,钙凝素-1、光感受器间类维甲酸结合蛋白和神经丝氨酸水平降低。生物通路分析显示玻璃体含有30种与钾likrein-kinin,凝血和补体系统相关的蛋白质。其中补体C3、补体因子1、凝血酶原、α -l-抗胰蛋白酶和抗凝血酶III在PDR玻璃体中较NDM玻璃体升高。在PDR玻璃体中检测到因子XII,而在NDM和noDR玻璃体中均未观察到因子XII。与noDR或NDM玻璃体相比,PDR玻璃体也有过氧化物还毒素-1水平升高和细胞外超氧化物歧化酶水平降低。这些数据提供了对人类玻璃体蛋白质组的深入分析,并揭示了与PDR相关的蛋白质改变。
An understanding of the diabetes-induced alterations in vitreous protein composition in the absence and in the presence of proliferative diabetic retinopathy (PDR) may provide insights into factors and mechanisms responsible for this disease. We have performed a comprehensive proteomic analysis and comparison of vitreous samples from individuals with diabetes but without diabetic retinopathy (noDR) or with PDR and nondiabetic individuals (NDM). Using preparative one-dimensional SIDS-PAGE and nano-LC/MS/MS of 17 independent vitreous samples, we identified 252 proteins from human vitreous. Fifty-six proteins were differentially abundant in noDR and PDR vitreous compared with NDM vitreous, including 32 proteins increased and 10 proteins decreased in PDR vitreous compared with NDM vitreous. Comparison of noDR and PDR groups revealed increased levels of angiotensinogen and decreased levels of calsyntenin-1, interphotoreceptor retinoid-binding protein, and neuroserpin in PDR vitreous. Biological pathway analysis revealed that vitreous contains 30 proteins associated with the kallikrein-kinin, coagulation, and complement systems. Five of them (complement C3, complement factor 1, prothrombin, alpha-l-antitrypsin, and antithrombin III) were increased in PDR vitreous compared with NDM vitreous. Factor XII was detected in PDR vitreous but not observed in either NDM or noDR vitreous. PDR vitreous also had increased levels of peroxiredoxin-1 and decreased levels of extracellular superoxide dismutase, compared with noDR or NDM vitreous. These data provide an in depth analysis of the human vitreous proteome and reveal protein alterations that are associated with PDR.