O-GlcNAc transferase deficiency aggravates the ferroptosis induced by pulmonary ischemia/reperfussion in mice
Objective:To investigate the influence of O-GlcNAc transferase(Ogt)deficiency on ischemia/reperfusion(I/R)-induced ferroptosis and the mechanism behind it.Methods:Twelve Ogt conditional knockout mice with tamoxifen treatment(Ogt-CKO)and 12 Ogt-conditional knockout mice without tamoxifen treatment(Ogtfl/fl),all aging from 6 to 8 weeks,were divided into four groups according to different treatments(sham treatment or I/R treatment):sham+Ogtfl/fl,I/R+Ogtfl/fl,sham+Ogt-CKO,and I/R+Ogt-CKO.The model of lung I/R was induced by occluding the left pulmonary hi-lum for 1 h followed by 4 h reperfusion.In the sham group,mice underwent left thoracotomies with-out I/R followed by ventilation for 5 h.The mice were sacrificed after 4 h reperfusion or 5 h ventila-tion.By using HE staining,lung tissue sections were observed under the light microscope,and the pathological injury scores were calculated.The morphology of cells was observed under the transmis-sion electron microscope.The level of ROS was identified by immunofluorescent staining.By using Western Blot,the expressions of SLC7A11,G6PDH,and Nrf2 were detected.Results:Compared with the group of sham+Ogtfl/fl,the pathological injury scores of lung tissue,the expression of G6PDH,Nrf2,and the production of ROS were increased,and the expression of SLC7A11 was de-creased.Moreover,smaller pulmonary epithelial cells and karyopyknosis occurred in I/R+Ogtfl/fl group.Compared with the I/R+Ogtfl/fl group,the pathological injury scores of lung tissue and the lev-els of ROS were markedly increased,the damages of epithelial cells were more obvious,and the ex-pression of SLC7A11,G6PDH,and Nrf2 were significantly decreased in I/R+Ogt-CKO group.Conclusion:Ogt deficiency aggravated pulmonary ischemia-reperfusion induced ferroptosis via Nrf2/G6PDH pathway.
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