Curcumin Attenuates Retinal Vascular Leakage by Inhibiting Calcium/Calmodulin-Dependent Protein Kinase II Activity in Streptozotocin-Induced Diabetes
Background: Curcumin possesses many pharmacological properties including anti-inflammatory effects. Although prior studies indicate that curcumin has beneficial effects for diabetic retinopathy, the mechanism of action is not known. To address this issue, we investigated the effect of curcumin again...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Cell Physiol Biochem Press GmbH & Co KG
2016-09-01
|
| Series: | Cellular Physiology and Biochemistry |
| Subjects: | |
| Online Access: | http://www.karger.com/Article/FullText/447826 |
| _version_ | 1818921617311399936 |
|---|---|
| author | Jun Li Peipei Wang Jia Ying Zhen Chen Songping Yu |
| author_facet | Jun Li Peipei Wang Jia Ying Zhen Chen Songping Yu |
| author_sort | Jun Li |
| collection | DOAJ |
| description | Background: Curcumin possesses many pharmacological properties including anti-inflammatory effects. Although prior studies indicate that curcumin has beneficial effects for diabetic retinopathy, the mechanism of action is not known. To address this issue, we investigated the effect of curcumin against diabetes-induced retinal vascular damage and its mechanism of action by using cultured retinal Müller cells stimulated with high glucose. Methods: We studied the effects of curcumin in vivo in the retinas of rats rendered diabetic by streptozotocin and in vitro in Müller cells stimulated with high glucose. We administered curcumin, or KN93, an inhibitor of calcium/calmodulin dependent protein kinase II (CaMKII), or saline vehicle to experimental animals on a daily basis for 12 weeks. Primary cultures of rat Müller cells were incubated with normal glucose or high glucose, with or without curcumin, KN93, or pyrrolidine dithiocarbamate (PDTC), an inhibitor of the transcription protein nuclear factor κB (NF-κB). We examined mRNA and protein levels of vascular endothelial growth factor (VEGF), inducible nitric oxide synthase (iNOS) and intercellular adhesion molecule-1 (ICAM-1) by real-time RT-PCR and Western blotting, respectively. Retinal levels of CaMKII and NF-κB were examined by Western blotting. Vascular leakage was evaluated using Evans blue. Results: Curcumin and KN93 significantly inhibited the activation of CaMKII/NF-κB signaling induced by diabetes or elevated glucose, and subsequently decreased the expression of VEGF, iNOS and ICAM-1. These changes were associated with a decrease of diabetes-induced retinal vascular leakage. Conclusion: Curcumin protects the diabetic rat retina against early retinal vascular damage, by inhibition of CaMKII activity. Curcumin is currently used to treat a number of clinical conditions, and may prove beneficial for the management of diabetic retinopathy. |
| first_indexed | 2024-12-20T01:40:29Z |
| format | Article |
| id | doaj.art-80b49918eb284741b47b1b6ef123a41e |
| institution | Directory Open Access Journal |
| issn | 1015-8987 1421-9778 |
| language | English |
| last_indexed | 2024-12-20T01:40:29Z |
| publishDate | 2016-09-01 |
| publisher | Cell Physiol Biochem Press GmbH & Co KG |
| record_format | Article |
| series | Cellular Physiology and Biochemistry |
| spelling | doaj.art-80b49918eb284741b47b1b6ef123a41e2022-12-21T19:57:54ZengCell Physiol Biochem Press GmbH & Co KGCellular Physiology and Biochemistry1015-89871421-97782016-09-013931196120810.1159/000447826447826Curcumin Attenuates Retinal Vascular Leakage by Inhibiting Calcium/Calmodulin-Dependent Protein Kinase II Activity in Streptozotocin-Induced DiabetesJun LiPeipei WangJia YingZhen ChenSongping YuBackground: Curcumin possesses many pharmacological properties including anti-inflammatory effects. Although prior studies indicate that curcumin has beneficial effects for diabetic retinopathy, the mechanism of action is not known. To address this issue, we investigated the effect of curcumin against diabetes-induced retinal vascular damage and its mechanism of action by using cultured retinal Müller cells stimulated with high glucose. Methods: We studied the effects of curcumin in vivo in the retinas of rats rendered diabetic by streptozotocin and in vitro in Müller cells stimulated with high glucose. We administered curcumin, or KN93, an inhibitor of calcium/calmodulin dependent protein kinase II (CaMKII), or saline vehicle to experimental animals on a daily basis for 12 weeks. Primary cultures of rat Müller cells were incubated with normal glucose or high glucose, with or without curcumin, KN93, or pyrrolidine dithiocarbamate (PDTC), an inhibitor of the transcription protein nuclear factor κB (NF-κB). We examined mRNA and protein levels of vascular endothelial growth factor (VEGF), inducible nitric oxide synthase (iNOS) and intercellular adhesion molecule-1 (ICAM-1) by real-time RT-PCR and Western blotting, respectively. Retinal levels of CaMKII and NF-κB were examined by Western blotting. Vascular leakage was evaluated using Evans blue. Results: Curcumin and KN93 significantly inhibited the activation of CaMKII/NF-κB signaling induced by diabetes or elevated glucose, and subsequently decreased the expression of VEGF, iNOS and ICAM-1. These changes were associated with a decrease of diabetes-induced retinal vascular leakage. Conclusion: Curcumin protects the diabetic rat retina against early retinal vascular damage, by inhibition of CaMKII activity. Curcumin is currently used to treat a number of clinical conditions, and may prove beneficial for the management of diabetic retinopathy.http://www.karger.com/Article/FullText/447826CurcuminRetinal vascular leakageCaMKIIDiabetic retinopathy |
| spellingShingle | Jun Li Peipei Wang Jia Ying Zhen Chen Songping Yu Curcumin Attenuates Retinal Vascular Leakage by Inhibiting Calcium/Calmodulin-Dependent Protein Kinase II Activity in Streptozotocin-Induced Diabetes Cellular Physiology and Biochemistry Curcumin Retinal vascular leakage CaMKII Diabetic retinopathy |
| title | Curcumin Attenuates Retinal Vascular Leakage by Inhibiting Calcium/Calmodulin-Dependent Protein Kinase II Activity in Streptozotocin-Induced Diabetes |
| title_full | Curcumin Attenuates Retinal Vascular Leakage by Inhibiting Calcium/Calmodulin-Dependent Protein Kinase II Activity in Streptozotocin-Induced Diabetes |
| title_fullStr | Curcumin Attenuates Retinal Vascular Leakage by Inhibiting Calcium/Calmodulin-Dependent Protein Kinase II Activity in Streptozotocin-Induced Diabetes |
| title_full_unstemmed | Curcumin Attenuates Retinal Vascular Leakage by Inhibiting Calcium/Calmodulin-Dependent Protein Kinase II Activity in Streptozotocin-Induced Diabetes |
| title_short | Curcumin Attenuates Retinal Vascular Leakage by Inhibiting Calcium/Calmodulin-Dependent Protein Kinase II Activity in Streptozotocin-Induced Diabetes |
| title_sort | curcumin attenuates retinal vascular leakage by inhibiting calcium calmodulin dependent protein kinase ii activity in streptozotocin induced diabetes |
| topic | Curcumin Retinal vascular leakage CaMKII Diabetic retinopathy |
| url | http://www.karger.com/Article/FullText/447826 |
| work_keys_str_mv | AT junli curcuminattenuatesretinalvascularleakagebyinhibitingcalciumcalmodulindependentproteinkinaseiiactivityinstreptozotocininduceddiabetes AT peipeiwang curcuminattenuatesretinalvascularleakagebyinhibitingcalciumcalmodulindependentproteinkinaseiiactivityinstreptozotocininduceddiabetes AT jiaying curcuminattenuatesretinalvascularleakagebyinhibitingcalciumcalmodulindependentproteinkinaseiiactivityinstreptozotocininduceddiabetes AT zhenchen curcuminattenuatesretinalvascularleakagebyinhibitingcalciumcalmodulindependentproteinkinaseiiactivityinstreptozotocininduceddiabetes AT songpingyu curcuminattenuatesretinalvascularleakagebyinhibitingcalciumcalmodulindependentproteinkinaseiiactivityinstreptozotocininduceddiabetes |