VEGF-B inhibits hyperglycemia- and Macugen-induced retinal apoptosis

Huang, Dongwei; Zhao, Chunxia; Ju, Rong; Kumar, Anil; Tian, Geng; Huang, Lijuan; Zheng, Lei; Li, Xianglin; Lixian, Liu; Wang, Shasha; Ren, Xianyue; Ye, Zhimin; Chen, Wei; Xing, Liying; Chen, Qishan; Gao, Zhiqin; Mi, Jia; Tang, Zhongshu; Wang, Bin; Zhang, Shuping; Lee, Chunsik; Li, Xuri

doi:10.1038/srep26059

Cited by 20 publications

(20 citation statements)

References 35 publications

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“…Type 1 diabetic model was induced as described previously52. Briefly, the SD rats were fasted overnight and received streptozotocin (STZ, Sigma-Aldrich, MO, USA, 50 mg/kg/d, i.p., dissolved in 0.1 mol/l citrate buffer, pH 4.5) injection for 3 consecutive days.…”

Section: Methodsmentioning

confidence: 99%

Melatonin ameliorates myocardial ischemia/reperfusion injury in type 1 diabetic rats by preserving mitochondrial function: role of AMPK-PGC-1α-SIRT3 signaling

Gong

Duan

et al. 2017

Sci Rep

175

137

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Enhancing mitochondrial biogenesis and reducing mitochondrial oxidative stress have emerged as crucial therapeutic strategies to ameliorate diabetic myocardial ischemia/reperfusion (MI/R) injury. Melatonin has been reported to be a safe and potent cardioprotective agent. However, its role on mitochondrial biogenesis or reactive oxygen species (ROS) production in type 1 diabetic myocardium and the underlying mechanisms remain unknown. We hypothesize that melatonin ameliorates MI/R injury in type 1 diabetic rats by preserving mitochondrial function via AMPK-PGC-1α-SIRT3 signaling pathway. Both our in vivo and in vitro data showed that melatonin reduced MI/R injury by improving cardiac function, enhancing mitochondrial SOD activity, ATP production and oxidative phosphorylation complex (II, III and IV), reducing myocardial apoptosis and mitochondrial MDA, H2O2 generation. Importantly, melatonin also activated AMPK-PGC-1α-SIRT3 signaling and increased SOD2, NRF1 and TFAM expressions. However, these effects were abolished by Compound C (a specific AMPK signaling blocker) administration. Additionally, our cellular experiment showed that SIRT3 siRNA inhibited the cytoprotective effect of melatonin without affecting p-AMPK/AMPK ratio and PGC-1α expression. Taken together, we concluded that melatonin preserves mitochondrial function by reducing mitochondrial oxidative stress and enhancing its biogenesis, thus ameliorating MI/R injury in type 1 diabetic state. AMPK-PGC1α-SIRT3 axis plays an essential role in this process.

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Section: Methodsmentioning

confidence: 99%

Melatonin ameliorates myocardial ischemia/reperfusion injury in type 1 diabetic rats by preserving mitochondrial function: role of AMPK-PGC-1α-SIRT3 signaling

Gong

Duan

et al. 2017

Sci Rep

175

137

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“…HREC cells were plated into 60 mm × 15 mm Petri dishes (2 × 10 5 cells per dish); after reaching 80% confluence, cells were shifted for 15 h to a low FBS medium (0.5% FBS). Cells were then cultured in medium (0.5% FBS) supplemented with physiological glucose concentration (5 mM) or with high levels of glucose (40 mM) ( Huang et al, 2016 ). Pharmacological treatment of HREC was carried out with 10 μM curcumin in high glucose medium for 24 h. The concentration of curcumin, used for experiments on HREC cells, was chosen on the basis of dose-response curve of curcumin for ROS production inhibition.…”

Section: Methodsmentioning

confidence: 99%

Retinal Protection and Distribution of Curcumin in Vitro and in Vivo

et al. 2018

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Diabetic retinopathy (DR), a secondary complication of diabetes, is a leading cause of irreversible blindness accounting for 5% of world blindness cases in working age. Oxidative stress and inflammation are considered causes of DR. Curcumin, a product with anti-oxidant and anti-inflammatory properties, is currently proposed as oral supplementation therapy for retinal degenerative diseases, including DR. In this study we predicted the pharmacodynamic profile of curcumin through an in silico approach. Furthermore, we tested the anti-oxidant and anti-inflammatory activity of curcumin on human retinal pigmented epithelial cells exposed to oxidative stress, human retinal endothelial and human retinal pericytes (HRPCs) cultured with high glucose. Because currently marketed curcumin nutraceutical products have not been so far evaluated for their ocular bioavailability; we assessed retinal distribution of curcumin, following oral administration, in rabbit eye. Curcumin (10 μM) decreased significantly (p < 0.01) ROS concentration and TNF-α release in retinal pigmented epithelial cells and retinal endothelial cells, respectively. The same curcumin concentration significantly (p < 0.01) protected retinal pericytes from high glucose damage as assessed by cell viability and LDH release. Among the tested formulations, only that containing a hydrophilic carrier provided therapeutic levels of curcumin in rabbit retina. In conclusion, our data suggest that curcumin, when properly formulated, may be of value in clinical practice to manage retinal diseases.

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“…In addition to cardiomyopathy, diabetic retinopathy is also a major consequence of diabetes and human retinal endothelial cells cultured in high glucose displayed decreased VEGFB gene expression ( 69 ). In rats made diabetic with 50 mg/kg STZ and injected with multiple intravitreal VEGFB injections 10 weeks later, TUNEL staining of the rat ganglion cell layer revealed a decrease in the number of apoptotic cells in the STZ animals treated with VEGFB ( 70 ).…”

Section: Vegfbmentioning

confidence: 99%

Vascular Endothelial Growth Factor B and Its Signaling

Lal¹,

Puri²,

Rodrigues³

2018

Front. Cardiovasc. Med.

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In diabetes, compromised glucose utilization leads the heart to use FA almost exclusively for ATP generation. Chronically, this adaptation unfortunately leads to the conversion of FA to potentially toxic FA metabolites. Paired with increased formation of reactive oxygen species related to excessive mitochondrial oxidation of FA, can provoke cardiac cell death. To protect against this cell demise, intrinsic mechanisms must be available to the heart. Vascular endothelial growth factor B (VEGFB) may be one growth factor that plays an important role in protecting against heart failure. As a member of the VEGF family, initial studies with VEGFB focused on its role in angiogenesis. Surprisingly, VEGFB does not appear to play a direct role in angiogenesis under normal conditions or even when overexpressed, but has been implicated in influencing vascular growth indirectly by affecting VEGFA action. Intriguingly, VEGFB has also been shown to alter gene expression of proteins involved in cardiac metabolism and promote cell survival. Conversely, multiple models of heart failure, including diabetic cardiomyopathy, have indicated a significant drop in VEGFB. In this review, we will discuss the biology of VEGFB, and its relationship to diabetic cardiomyopathy.

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VEGF-B inhibits hyperglycemia- and Macugen-induced retinal apoptosis

Cited by 20 publications

References 35 publications

Melatonin ameliorates myocardial ischemia/reperfusion injury in type 1 diabetic rats by preserving mitochondrial function: role of AMPK-PGC-1α-SIRT3 signaling

Melatonin ameliorates myocardial ischemia/reperfusion injury in type 1 diabetic rats by preserving mitochondrial function: role of AMPK-PGC-1α-SIRT3 signaling

Retinal Protection and Distribution of Curcumin in Vitro and in Vivo

Vascular Endothelial Growth Factor B and Its Signaling

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