title: Comparative proteomic analysis of histone post-translational modifications upon ischemia/reperfusion-induced retinal injury.
abstract: We present a detailed quantitative map of single and coexisting histone post-translational modifications (PTMs) in rat retinas affected by ischemia and reperfusion (I/R) injury. Retinal I/R injury contributes to serious ocular diseases, which can lead to vision loss and blindness. We applied linear ion trap-orbitrap hybrid tandem mass spectrometry (MS/MS) to quantify 131 single histone marks and 143 combinations of multiple histone marks in noninjured and injured retinas. We observed 34 histone PTMs that exhibited significantly (p < 0.05) different abundance between healthy and I/R injured eyes, of which we confirmed three H4 histone marks by Western blotting. H4K20me2 was up to 4-fold change up-regulated after the injury and is associated with the response to DNA damage as demonstrated by an increase in the phosphorylation of p53 and Chk1. This study demonstrates that quantitative MS provides a sensitive and accurate way to dissect the changes in the histone code after retinal injury. Specifically, DNA damage associated histone PTMs may contribute to neurovascular degeneration during the process of ischemia/reperfusion injury.
authors.affiliation: College of Life Sciences, Wuhan University , Wuhan 430072, P. R. China.
authors.forename: Xiaolu
authors.initials: X
authors.lastname: Zhao
authors.forename: Simone
authors.initials: S
authors.lastname: Sidoli
authors.forename: Leilei
authors.initials: L
authors.lastname: Wang
authors.forename: Wenjun
authors.initials: W
authors.lastname: Wang
authors.forename: Lin
authors.initials: L
authors.lastname: Guo
authors.forename: Ole N
authors.initials: ON
authors.lastname: Jensen
authors.forename: Ling
authors.initials: L
authors.lastname: Zheng
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D006657:Histones / Q000032:analysis / Q000737:chemistry / Q000378:metabolism; D008297:Male; D008969:Molecular Sequence Data; D011499:Protein Processing, Post-Translational; D020543:Proteome / Q000032:analysis / Q000737:chemistry / Q000378:metabolism; D040901:Proteomics / Q000379:methods; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000378:metabolism*; D012160:Retina / Q000737:chemistry / Q000293:injuries / Q000378:metabolism
chemical_list: D006657:Histones; D020543:Proteome