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Soluble Vascular Adhesion Protein-1 Mediates Spermine Oxidation as Semicarbazide-Sensitive Amine Oxidase : Possible Role in Proliferative Diabetic Retinopathy

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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
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:
Type: article (author version)
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)

Submitter: 村田 美幸

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