High-Mobility Group Box-1 Induces Decreased Brain-Derived Neurotrophic Factor-Mediated Neuroprotection in the Diabetic Retina
To test the hypothesis that brain-derived neurotrophic factor-(BDNF-) mediated neuroprotection is reduced by high-mobility group box-1 (HMGB1) in diabetic retina, paired vitreous and serum samples from 46 proliferative diabetic retinopathy and 34 nondiabetic patients were assayed for BDNF, HMGB1, so...
Saved in:
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2013-01-01
|
| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2013/863036 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832558292204781568 |
|---|---|
| author | Ahmed M. Abu El-Asrar Mohd Imtiaz Nawaz Mohammad Mairaj Siddiquei Abdullah S. Al-Kharashi Dustan Kangave Ghulam Mohammad |
| author_facet | Ahmed M. Abu El-Asrar Mohd Imtiaz Nawaz Mohammad Mairaj Siddiquei Abdullah S. Al-Kharashi Dustan Kangave Ghulam Mohammad |
| author_sort | Ahmed M. Abu El-Asrar |
| collection | DOAJ |
| description | To test the hypothesis that brain-derived neurotrophic factor-(BDNF-) mediated neuroprotection is reduced by high-mobility group box-1 (HMGB1) in diabetic retina, paired vitreous and serum samples from 46 proliferative diabetic retinopathy and 34 nondiabetic patients were assayed for BDNF, HMGB1, soluble receptor for advanced glycation end products (sRAGE), soluble intercellular adhesion molecule-1 (sICAM-1), monocyte chemoattractant protein-1 (MCP-1), and TBARS. We also examined retinas of diabetic and HMGB1 intravitreally injected rats. The effect of the HMGB1 inhibitor glycyrrhizin on diabetes-induced changes in retinal BDNF expressions was studied. Western blot, ELISA, and TBARS assays were used. BDNF was not detected in vitreous samples. BDNF levels were significantly lower in serum samples from diabetic patients compared with nondiabetics, whereas HMGB1, sRAGE, sICAM-1, and TBARS levels were significantly higher in diabetic serum samples. MCP-1 levels did not differ significantly. There was significant inverse correlation between serum levels of BDNF and HMGB1. Diabetes and intravitreal administration of HMGB1 induced significant upregulation of the expression of HMGB1, TBARS, and cleaved caspase-3, whereas the expression of BDNF and synaptophysin was significantly downregulated in rat retinas. Glycyrrhizin significantly attenuated diabetes-induced downregulation of BDNF. Our results suggest that HMGB1-induced downregulation of BDNF might be involved in pathogenesis of diabetic retinal neurodegeneration. |
| format | Article |
| id | doaj-art-1243650814a841ecbdfe19053ee008b9 |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2013-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-1243650814a841ecbdfe19053ee008b92025-02-03T01:32:40ZengWileyMediators of Inflammation0962-93511466-18612013-01-01201310.1155/2013/863036863036High-Mobility Group Box-1 Induces Decreased Brain-Derived Neurotrophic Factor-Mediated Neuroprotection in the Diabetic RetinaAhmed M. Abu El-Asrar0Mohd Imtiaz Nawaz1Mohammad Mairaj Siddiquei2Abdullah S. Al-Kharashi3Dustan Kangave4Ghulam Mohammad5Department of Ophthalmology, College of Medicine, King Saud University, King Abdulaziz University Hospital, Old Airport Road, P.O. Box 245, Riyadh 11411, Saudi ArabiaDepartment of Ophthalmology, College of Medicine, King Saud University, King Abdulaziz University Hospital, Old Airport Road, P.O. Box 245, Riyadh 11411, Saudi ArabiaDepartment of Ophthalmology, College of Medicine, King Saud University, King Abdulaziz University Hospital, Old Airport Road, P.O. Box 245, Riyadh 11411, Saudi ArabiaDepartment of Ophthalmology, College of Medicine, King Saud University, King Abdulaziz University Hospital, Old Airport Road, P.O. Box 245, Riyadh 11411, Saudi ArabiaDepartment of Ophthalmology, College of Medicine, King Saud University, King Abdulaziz University Hospital, Old Airport Road, P.O. Box 245, Riyadh 11411, Saudi ArabiaDepartment of Ophthalmology, College of Medicine, King Saud University, King Abdulaziz University Hospital, Old Airport Road, P.O. Box 245, Riyadh 11411, Saudi ArabiaTo test the hypothesis that brain-derived neurotrophic factor-(BDNF-) mediated neuroprotection is reduced by high-mobility group box-1 (HMGB1) in diabetic retina, paired vitreous and serum samples from 46 proliferative diabetic retinopathy and 34 nondiabetic patients were assayed for BDNF, HMGB1, soluble receptor for advanced glycation end products (sRAGE), soluble intercellular adhesion molecule-1 (sICAM-1), monocyte chemoattractant protein-1 (MCP-1), and TBARS. We also examined retinas of diabetic and HMGB1 intravitreally injected rats. The effect of the HMGB1 inhibitor glycyrrhizin on diabetes-induced changes in retinal BDNF expressions was studied. Western blot, ELISA, and TBARS assays were used. BDNF was not detected in vitreous samples. BDNF levels were significantly lower in serum samples from diabetic patients compared with nondiabetics, whereas HMGB1, sRAGE, sICAM-1, and TBARS levels were significantly higher in diabetic serum samples. MCP-1 levels did not differ significantly. There was significant inverse correlation between serum levels of BDNF and HMGB1. Diabetes and intravitreal administration of HMGB1 induced significant upregulation of the expression of HMGB1, TBARS, and cleaved caspase-3, whereas the expression of BDNF and synaptophysin was significantly downregulated in rat retinas. Glycyrrhizin significantly attenuated diabetes-induced downregulation of BDNF. Our results suggest that HMGB1-induced downregulation of BDNF might be involved in pathogenesis of diabetic retinal neurodegeneration.http://dx.doi.org/10.1155/2013/863036 |
| spellingShingle | Ahmed M. Abu El-Asrar Mohd Imtiaz Nawaz Mohammad Mairaj Siddiquei Abdullah S. Al-Kharashi Dustan Kangave Ghulam Mohammad High-Mobility Group Box-1 Induces Decreased Brain-Derived Neurotrophic Factor-Mediated Neuroprotection in the Diabetic Retina Mediators of Inflammation |
| title | High-Mobility Group Box-1 Induces Decreased Brain-Derived Neurotrophic Factor-Mediated Neuroprotection in the Diabetic Retina |
| title_full | High-Mobility Group Box-1 Induces Decreased Brain-Derived Neurotrophic Factor-Mediated Neuroprotection in the Diabetic Retina |
| title_fullStr | High-Mobility Group Box-1 Induces Decreased Brain-Derived Neurotrophic Factor-Mediated Neuroprotection in the Diabetic Retina |
| title_full_unstemmed | High-Mobility Group Box-1 Induces Decreased Brain-Derived Neurotrophic Factor-Mediated Neuroprotection in the Diabetic Retina |
| title_short | High-Mobility Group Box-1 Induces Decreased Brain-Derived Neurotrophic Factor-Mediated Neuroprotection in the Diabetic Retina |
| title_sort | high mobility group box 1 induces decreased brain derived neurotrophic factor mediated neuroprotection in the diabetic retina |
| url | http://dx.doi.org/10.1155/2013/863036 |
| work_keys_str_mv | AT ahmedmabuelasrar highmobilitygroupbox1inducesdecreasedbrainderivedneurotrophicfactormediatedneuroprotectioninthediabeticretina AT mohdimtiaznawaz highmobilitygroupbox1inducesdecreasedbrainderivedneurotrophicfactormediatedneuroprotectioninthediabeticretina AT mohammadmairajsiddiquei highmobilitygroupbox1inducesdecreasedbrainderivedneurotrophicfactormediatedneuroprotectioninthediabeticretina AT abdullahsalkharashi highmobilitygroupbox1inducesdecreasedbrainderivedneurotrophicfactormediatedneuroprotectioninthediabeticretina AT dustankangave highmobilitygroupbox1inducesdecreasedbrainderivedneurotrophicfactormediatedneuroprotectioninthediabeticretina AT ghulammohammad highmobilitygroupbox1inducesdecreasedbrainderivedneurotrophicfactormediatedneuroprotectioninthediabeticretina |