ROS-induced Oxidative Injury involved in Pathogenesis of Fungal Keratitis via p38 MAPK Activation.
ROS-induced Oxidative Injury involved in Pathogenesis of Fungal Keratitis via p38 MAPK Activation.
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ROS 诱导的氧化损伤通过 p38 MAPK 激活参与真菌性角膜炎的发病机制
DOI：
10.1038/s41598-017-09636-w
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发表时间：
2017-09-05
影响因子：
4.6
通讯作者：
Yuan X
中科院分区：
文献类型：
--
作者：
Hua X;Chi W;Su L;Li J;Zhang Z;Yuan X
本研究采用小鼠活体角膜炎模型和人角膜上皮细胞体外培养模型，探讨ROS诱导的氧化应激在真菌性角膜炎发病中的作用机制。与正常对照组小鼠和HECs相比，暴露于白色念珠菌的真菌角膜和HECs中ROS的产生显著增加，并伴随着p38丝裂原活化蛋白激酶(MAPK)的激活。真菌感染的角膜和内皮细胞中氧化标记物丙二醛(MDA)、4-羟基壬烯醛(HNE)、线粒体DNA 8-OHdG和乌头酸酶-2的产物增加。真菌感染还增加了血红素加氧酶-1(Hmox1)和环氧合酶-2(COX2)的mRNA表达和蛋白产量，而抗氧化酶超氧化物歧化酶-1(SOD1)、谷胱甘肽过氧化物酶-1(GPX1)和过氧化还蛋白-4(PRDX4)的水平受到抑制。有趣的是，共培养的p38抑制剂SB203580显著降低ROS、氧化标记物和加氧酶的水平。此外，SB203580还恢复了被真菌抑制的抗氧化酶水平。本研究首次证实ROS诱导的氧化损伤通过p38MAPK通路参与真菌性角膜炎的发病过程，为真菌性角膜炎的潜在治疗提供了新的治疗靶点。
This study was to explore the mechanism by which reactive oxygen species (ROS)-induced oxidative stress involved in the pathogenesis of fungal keratitis using anin vivoexperimental keratitis mouse model and anin vitroculture model of human corneal epithelial cells (HCECs). Compared to normal control mice and HCECs, ROS production was markedly increased in fungal corneas and HCECs exposed toCandida albicans, accompanied by p38 mitogen-activated protein kinases (MAPK) activation. Increased products of oxidative markers, malondialdehyde (MDA), 4–hydroxynonenal (HNE), mitochondria DNA 8-OHdG and aconitase-2 were observed in fungal infected corneas and HCECs. Fungal infection also increased the mRNA expression and protein production of heme oxygenase-1 (HMOX1) and cyclooxygenase-2 (COX2), with suppressed levels of antioxidant enzymes, superoxide dismutase-1 (SOD1), glutathione peroxidase-1 (GPx1) and peroxiredoxin-4 (PRDX4). Interestingly, the levels of ROS, oxidative markers and oxygenases were significantly reduced by co-cultured p38 inhibitor SB203580. Furthermore, SB203580 restored the levels of antioxidant enzymes suppressed by fungus. Our findings demonstrated for the first time that ROS-induced oxidative injury is involved in pathogenesis of fungal keratitis via p38 MAPK pathway, suggesting the novel therapeutic targets for the potential treatment of fungal keratitis.
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DOI：
10.1016/0027-5107(93)90158-c
发表时间：
1993-12-01
期刊：
MUTATION RESEARCH
影响因子：
--
作者：
ECKL, PM;ORTNER, A;ESTERBAUER, H
通讯作者：
ESTERBAUER, H
影响因子：
3.4
作者：
Kim, HS;Song, XJ;Li, DQ
通讯作者：
Li, DQ
影响因子：
3.3
作者：
Lambert, G. P.
通讯作者：
Lambert, G. P.
DOI：
10.1083/jcb.201102095
发表时间：
2011-07-11
期刊：
The Journal of cell biology
影响因子：
--
作者：
Finkel T
通讯作者：
Finkel T
影响因子：
3.7
作者：
Clauzure M;Valdivieso AG;Massip Copiz MM;Schulman G;Teiber ML;Santa-Coloma TA
通讯作者：
Santa-Coloma TA