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富马酸二甲酯的一种新型衍生物可促进葡萄糖受损的角膜再上皮化。

Glucose-impaired Corneal Re-epithelialization Is Promoted by a Novel Derivate of Dimethyl Fumarate.

作者信息

Giurdanella Giovanni, Longo Anna, Salerno Loredana, Romeo Giuseppe, Intagliata Sebastiano, Lupo Gabriella, Distefano Alfio, Platania Chiara Bianca Maria, Bucolo Claudio, Li Volti Giovanni, Anfuso Carmelina Daniela, Pittalà Valeria

机构信息

Department of Biomedical and Biotechnological Sciences, Section of Medical Biochemistry, University of Catania, Via S. Sofia 97, 95123 Catania, Italy.

Department of Drug and Health Sciences, University of Catania, 95125 Catania, Italy.

出版信息

Antioxidants (Basel). 2021 May 22;10(6):831. doi: 10.3390/antiox10060831.

DOI:10.3390/antiox10060831
PMID:34067436
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8224583/
Abstract

Glucose induces corneal epithelial dysfunctions characterized by delayed wound repair. Nuclear erythroid 2-related factor 2 (Nrf2) mediates cell protection mechanisms even through the Heme oxygenase-1 (HO-1) up-regulation. Here, we synthesized new HO-1 inducers by modifying dimethyl fumarate (DMF) and used docking studies to select VP13/126 as a promising compound with the best binding energy to Kelch-like ECH-associated protein 1 (keap1), which is the the regulator of Nrf2 nuclear translocation. We verified if VP13/126 protects SIRC cells from hyperglycemia compared to DMF. SIRC were cultured in normal (5 mM) or high glucose (25 mM, HG) in presence of DMF (1-25 μM) or VP13/126 (0.1-5 μM) with or without ERK1/2 inhibitor PD98059 (15 μM). VP13/126 was more effective than DMF in the prevention of HG-induced reduction of cell viability and proliferation. Reduction of wound closure induced by HG was similarly counteracted by 1 μM VP13/126 and 10 μM DMF. VP13/126 strongly increased phospho/total ERK1/2 and restored HO-1 protein in HG-treated SIRC; these effects are completely counteracted by PD98059. Moreover, high-content screening analysis showed a higher rate of Nrf2 nuclear translocation induced by VP13/126 than DMF in HG-stimulated SIRC. These data indicate that VP13/126 exerts remarkable pro-survival properties in HG-stimulated SIRC, promoting the Nrf2/HO-1 axis.

摘要

葡萄糖会引发以伤口修复延迟为特征的角膜上皮功能障碍。核红细胞2相关因子2（Nrf2）即使通过上调血红素加氧酶-1（HO-1）来介导细胞保护机制。在此，我们通过修饰富马酸二甲酯（DMF）合成了新的HO-1诱导剂，并利用对接研究选择VP13/126作为与Nrf2核转位调节因子kelch样ECH相关蛋白1（keap1）具有最佳结合能的有前景的化合物。我们验证了与DMF相比，VP13/126是否能保护SIRC细胞免受高血糖的影响。SIRC细胞在正常（5 mM）或高糖（25 mM，HG）环境中培养，同时存在DMF（1-25 μM）或VP13/126（0.1-5 μM），并添加或不添加ERK1/2抑制剂PD98059（15 μM）。在预防HG诱导的细胞活力和增殖降低方面，VP13/126比DMF更有效。1 μM VP13/126和10 μM DMF同样能抵消HG诱导的伤口愈合减少。VP13/126能显著增加HG处理的SIRC细胞中磷酸化/总ERK1/2水平并恢复HO-1蛋白；这些作用被PD98059完全抵消。此外，高内涵筛选分析表明，在HG刺激的SIRC细胞中，VP13/126诱导的Nrf2核转位率高于DMF。这些数据表明，VP13/126在HG刺激的SIRC细胞中具有显著的促生存特性，可促进Nrf2/HO-1轴的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d5f/8224583/d291be539792/antioxidants-10-00831-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d5f/8224583/1331b751cf93/antioxidants-10-00831-sch001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d5f/8224583/085878623a18/antioxidants-10-00831-sch002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d5f/8224583/e5fcdbca220e/antioxidants-10-00831-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d5f/8224583/49afd8a1c34c/antioxidants-10-00831-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d5f/8224583/d519c0222fdb/antioxidants-10-00831-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d5f/8224583/db74d2dbd899/antioxidants-10-00831-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d5f/8224583/1162f3486515/antioxidants-10-00831-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d5f/8224583/d291be539792/antioxidants-10-00831-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d5f/8224583/1331b751cf93/antioxidants-10-00831-sch001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d5f/8224583/085878623a18/antioxidants-10-00831-sch002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d5f/8224583/e5fcdbca220e/antioxidants-10-00831-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d5f/8224583/49afd8a1c34c/antioxidants-10-00831-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d5f/8224583/d519c0222fdb/antioxidants-10-00831-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d5f/8224583/db74d2dbd899/antioxidants-10-00831-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d5f/8224583/1162f3486515/antioxidants-10-00831-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d5f/8224583/d291be539792/antioxidants-10-00831-g006.jpg

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4
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