The Retinal Proteome in Experimental Diabetic Retinopathy
| Autor: | Patrice Fort, Willard M. Freeman, Thomas W. Gardner, Ravi S.J. Singh, Mandy K. Losiewicz |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
medicine.medical_specialty
Insulin medicine.medical_treatment Retinal Diabetic retinopathy Biology medicine.disease Proteomics Bioinformatics Biochemistry eye diseases Analytical Chemistry chemistry.chemical_compound Endocrinology chemistry Downregulation and upregulation Crystallin Diabetes mellitus Internal medicine medicine sense organs Molecular Biology Protein kinase B |
| Zdroj: | Molecular & Cellular Proteomics. 8:767-779 |
| ISSN: | 1535-9476 |
| DOI: | 10.1074/mcp.m800326-mcp200 |
| Popis: | Diabetic retinopathy is the leading cause of blindness in working age persons. Targeted studies have uncovered several components of the pathophysiology of the disease without unveiling the basic mechanisms. This study describes the use of complementary proteomic and genomic discovery methods that revealed that the proteins of the crystallin superfamily are increased dramatically in early diabetic retinopathy. Orthogonal methods confirmed that the amplitude of the up-regulation is greater than other changes described so far in diabetic retinopathy. A detailed time course study during diabetes showed differential up-regulation of the different isoforms of the crystallins superfamily. α- and β-crystallins were regulated primarily at the translation level, whereas γ-crystallins were also regulated transcriptionally. We also demonstrated cell-specific patterns of expression of the different crystallins in normal and diabetic rat retinas. In addition, systemic and periocular insulin treatments restored retinal crystallin protein expression during diabetes, indicating effects of phosphoinositide 3-kinase/Akt activity. Altogether this work shows the importance of proteomics discovery methods coupled with targeted approaches to unveil new disease mechanistic details and therapeutic targets. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
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