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氧化应激诱导的 FABP5 S-谷胱甘肽化通过抑制巨噬细胞炎症反应来保护急性肺损伤。

Oxidative stress-induced FABP5 S-glutathionylation protects against acute lung injury by suppressing inflammation in macrophages.

机构信息

Department of Pathology and Pathophysiology and Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, 310058, Hangzhou, P.R. China.

Institute of Immunology, Zhejiang University School of Medicine, 310058, Hangzhou, P.R. China.

出版信息

Nat Commun. 2021 Dec 7;12(1):7094. doi: 10.1038/s41467-021-27428-9.

DOI:10.1038/s41467-021-27428-9
PMID:34876574
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8651733/
Abstract

Oxidative stress contributes to the pathogenesis of acute lung injury. Protein S-glutathionylation plays an important role in cellular antioxidant defense. Here we report that the expression of deglutathionylation enzyme Grx1 is decreased in the lungs of acute lung injury mice. The acute lung injury induced by hyperoxia or LPS is significantly relieved in Grx1 KO and Grx1LysM mice, confirming the protective role of Grx1-regulated S-glutathionylation in macrophages. Using a quantitative redox proteomics approach, we show that FABP5 is susceptible to S-glutathionylation under oxidative conditions. S-glutathionylation of Cys127 in FABP5 promotes its fatty acid binding ability and nuclear translocation. Further results indicate S-glutathionylation promotes the interaction of FABP5 and PPARβ/δ, activates PPARβ/δ target genes and suppresses the LPS-induced inflammation in macrophages. Our study reveals a molecular mechanism through which FABP5 S-glutathionylation regulates macrophage inflammation in the pathogenesis of acute lung injury.

摘要

氧化应激导致急性肺损伤的发病机制。蛋白质 S-谷胱甘肽化在细胞抗氧化防御中起着重要作用。在这里，我们报告说，在急性肺损伤小鼠的肺部，去谷胱甘肽酶 Grx1 的表达减少。Grx1 KO 和 Grx1LysM 小鼠的高氧或 LPS 诱导的急性肺损伤明显缓解，证实了 Grx1 调节的 S-谷胱甘肽化在巨噬细胞中的保护作用。使用定量氧化还原蛋白质组学方法，我们表明 FABP5 在氧化条件下易发生 S-谷胱甘肽化。FABP5 中 Cys127 的 S-谷胱甘肽化促进其脂肪酸结合能力和核易位。进一步的结果表明，S-谷胱甘肽化促进 FABP5 和 PPARβ/δ 的相互作用，激活 PPARβ/δ 靶基因，并抑制巨噬细胞中 LPS 诱导的炎症。我们的研究揭示了一种分子机制，通过该机制，FABP5 的 S-谷胱甘肽化调节急性肺损伤发病机制中巨噬细胞的炎症。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8265/8651733/cce1bb600f49/41467_2021_27428_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8265/8651733/6d52d9ff8f13/41467_2021_27428_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8265/8651733/c0a92fcde670/41467_2021_27428_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8265/8651733/c0c163e497fa/41467_2021_27428_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8265/8651733/731328dfb593/41467_2021_27428_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8265/8651733/8ecd949d164f/41467_2021_27428_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8265/8651733/4e12bf098813/41467_2021_27428_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8265/8651733/be7cdaa98bf3/41467_2021_27428_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8265/8651733/cce1bb600f49/41467_2021_27428_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8265/8651733/6d52d9ff8f13/41467_2021_27428_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8265/8651733/c0a92fcde670/41467_2021_27428_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8265/8651733/c0c163e497fa/41467_2021_27428_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8265/8651733/731328dfb593/41467_2021_27428_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8265/8651733/8ecd949d164f/41467_2021_27428_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8265/8651733/4e12bf098813/41467_2021_27428_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8265/8651733/be7cdaa98bf3/41467_2021_27428_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8265/8651733/cce1bb600f49/41467_2021_27428_Fig8_HTML.jpg

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