Hydroxyproline alleviates 4-hydroxy-2-nonenal-induced DNA damage and apoptosis in porcine intestinal epithelial cells  

作　　者：Yun Ji Yu He Ying Yang Zhaolai Dai Zhenlong Wu 

机构地区：[1]State Key Laboratory of Animal Nutrition,Department of Animal Nutrition and Feed Science,China Agricultural University,Beijing 100193,China [2]Beijing Advanced Innovation Center for Food Nutrition and Human Health,China Agricultural University,Beijing 100193,China

出　　处：《Animal Nutrition》2022年第2期7-15,共9页动物营养（英文版）

基　　金：the National Natural Science Foundation of China(No.31625025,31301979);the Zhengzhou 1125 Talent Program,and the Jinxinnong Animal Science Development Foundation.

摘　　要：Oxidative stress has been confirmed in relation to intestinal mucosa damage and multiple bowel diseases.Hydroxyproline (Hyp) is an imino acid abundant in sow's milk. Compelling evidence has beengathered showing the potential antioxidative properties of Hyp. However, the role and mechanism ofHyp in porcine intestinal epithelial cells in response to oxidative stress remains unknown. In this study,small intestinal epithelial cell lines of piglets (IPEC-1) were used to evaluate the protective effects of Hypon 4-hydroxy-2-nonenal (4-HNE)-induced oxidative DNA damage and apoptosis. IPEC-1 pretreated with0.5 to 5 mmol/L Hyp were exposed to 4-HNE (40 mmol/L) in the presence or absence of Hyp. Thereafter,the cells were subjected to apoptosis detection by Hoechst staining, flow cytometry, and Western blot orDNA damage analysis by comet assay, immunofluorescence, and reverse-transcription quantitative PCR(RT-qPCR). Cell apoptosis and the upregulation of cleaved-caspase-3 induced by 4-HNE (40 mmol/L) wereinhibited by 5 mmol/L of Hyp. In addition, 5 mmol/L Hyp attenuated 4-HNE-induced reactive oxygenspecies (ROS) accumulation, glutathione (GSH) deprivation and DNA damage. The elevation in transcriptionof GADD45a (growth arrest and DNA-damage-inducible protein 45 alpha) and GADD45b(growth arrest and DNA-damage-inducible protein 45 beta), as well as the phosphorylation of H2AX(H2A histone family, member X), p38 MAPK (mitogen-activated protein kinase), and JNK (c-Jun N-terminalkinase) in cells treated with 4-HNE were alleviated by 5 mmol/L Hyp. Furthermore, Hyp supplementationincreased the protein abundance of Krüppel like factor 4 (KLF4) in cells exposed to 4-HNE.Suppression of KLF4 expression by kenpaulone impeded the resistance of Hyp-treated cells to DNAdamage and apoptosis induced by 4-HNE. Collectively, our results indicated that Hyp serves to protectagainst 4-HNE-induced apoptosis and DNA damage in IPEC-1 cells, which is partially pertinent with theenhanced expression of KLF4. Our data provides an updated explanation for

关 键 词：HYDROXYPROLINE APOPTOSIS DNA damage 4-Hydroxy-2-nonenal Oxidative stress 

分 类 号：S828.5[农业科学—畜牧学]