| Title: | Soluble Vascular Adhesion Protein-1 Mediates Spermine Oxidation as Semicarbazide-Sensitive Amine Oxidase : Possible Role in Proliferative Diabetic Retinopathy |
| Other Titles: | Acrolein Production by VAP-1/SSAO |
| Authors: | Murata, Miyuki Browse this author |
| Noda, Kousuke Browse this author →KAKEN DB |
| Kawasaki, Akiko Browse this author |
| Yoshida, Shiho Browse this author |
| Dong, Yoko Browse this author |
| Saito, Michiyuki Browse this author |
| Dong, Zhenyu Browse this author |
| Ando, Ryo Browse this author |
| Mori, Shohei Browse this author |
| Saito, Wataru Browse this author →KAKEN DB |
| Kanda, Atsuhiro Browse this author →KAKEN DB |
| Ishida, Susumu Browse this author →KAKEN DB |
| Keywords: | Acrolein |
| diabetic retinopathy |
| hydrogen peroxide |
| oxidative stress |
| polyamine |
| Issue Date: | 2017 |
| Publisher: | Taylor & Francis |
| Journal Title: | Current eye research |
| Volume: | 42 |
| Issue: | 12 |
| Start Page: | 1674 |
| End Page: | 1683 |
| Publisher DOI: | 10.1080/02713683.2017.1359847 |
| PMID: | 28937866 |
| Abstract: | Purpose/Aim of the study: To explore the possible role of vascular adhesion protein-1 (VAP-1) via its enzymatic function as a semicarbazide-sensitive amine oxidase (SSAO) in the pathogenesis of proliferative diabetic retinopathy (PDR). Materials and Methods: The levels of soluble VAP-1/SSAO and the unsaturated aldehyde acrolein (ACR)-conjugated protein, Nε-(3-formyl-3, 4-dehydropiperidino) lysine adduct (FDP-Lys), were measured in vitreous fluid samples of PDR and non-diabetic patients using ELISA. Recombinant human VAP-1/SSAO (rhVAP-1/SSAO) was incubated with spermine, with or without semicarbazide or RTU-1096 (a specific inhibitor for VAP-1/SSAO). Immunofluorescence assays were performed to assess the localization of VAP-1/SSAO and FDP-Lys in fibrovascular tissues from patients with PDR. The impact of ACR on cultured retinal capillary endothelial cells was assessed using a cell viability assay and total glutathione (GSH) measurements. Results: The levels of sVAP-1/SSAO and FDP-Lys were elevated in the vitreous fluid of patients with PDR. Incubation of rhVAP-1 with spermine resulted in the generation of hydrogen peroxide and FDP-Lys and the production was inhibited by semicarbazide and RTU-1096. In fibrovascular tissues, FDP-Lys and VAP-1/SSAO were present in endothelial cells. ACR stimulation reduced GSH levels in the cultured endothelial cells in a dose-dependent manner and caused cellular toxicity. Conclusions: Our results indicate the pathological role of sVAP-1/SSAO to generate hydrogen peroxide and toxic aldehyde ACR, both of which are associated with oxidative stress, as a consequence of spermine oxidation in eyes with PDR. |
| Rights: | This is an Accepted Manuscript of an article published by Taylor & Francis in Current Eye Research in 2017, available online: http://www.tandfonline.com/10.1080/02713683.2017.1359847. |
| Type: | article (author version) |
| URI: | http://hdl.handle.net/2115/72074 |
| Appears in Collections: | 医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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