TAT-mediated peroxiredoxin 5 and 6 protein transduction protects against high-glucose-induced cytotoxicity in retinal pericytes
| Autor: | Dhirendra P. Singh, Eri Kubo, Yoshio Akagi, Nigar Fatma |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Swine
DNA damage Apoptosis Biology medicine.disease_cause Retina General Biochemistry Genetics and Molecular Biology Rats Sprague-Dawley Transduction (genetics) Transduction Genetic medicine Animals Humans General Pharmacology Toxicology and Pharmaceutics Cells Cultured chemistry.chemical_classification Reactive oxygen species Peroxiredoxins General Medicine Recombinant Proteins Rats Cell biology Blot Glucose medicine.anatomical_structure chemistry Biochemistry HIV-1 Female tat Gene Products Human Immunodeficiency Virus Pericyte Pericytes Peroxiredoxin Oxidative stress Peroxiredoxin VI |
| Zdroj: | Life Sciences. 84:857-864 |
| ISSN: | 0024-3205 |
| DOI: | 10.1016/j.lfs.2009.03.019 |
| Popis: | Aims Hyperglycemia-induced oxidative stress is implicated in pericyte apoptosis seen in diabetic retinopathy. The six mammalian Peroxiredoxins (PRDXs) comprise a novel family of antioxidative proteins that negatively regulate oxidative stress-induced apoptosis by controlling reactive oxygen species (ROS) levels. Main methods Sprague–Dawley rats were used to detect the retinal expressions of PRDXs1–6. Pig pericytes cultured in high-glucose medium were used to monitor the protective effect of PRDX5 and 6 against high-glucose-associated change. Recombinant PRDX5 and 6 proteins were linked to the Trans-Activating Transduction (TAT) domain from HIV-1 TAT protein for their efficient delivery into cells/tissues. Key findings We found higher expression of PRDX5 and 6 mRNAs and PRDX5 and 6 proteins in retina than the other Prdxs (Prdx1–4). Western blotting affirmed the intracellular presence of TAT-linked proteins and revealed the efficient transduction of TAT-HA-PRDX5 and 6 in these cells. Extrinsic supply of TAT-HA-PRDX5 and 6 proteins inhibited the oxidative stress-induced DNA damage after high-glucose exposure in pig pericytes. The cell survival and apoptosis assay revealed that extrinsic supply of TAT-HA-PRDX5 and 6 proteins was responsible for inhibiting hyperglycemia-induced pericyte apoptosis. Significance Results suggest that delivery of PRDX5 and 6 might protect hyperglycemia-induced pericyte loss to inhibit oxidative stress. |
| Databáze: | OpenAIRE |
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