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

• Murata, Miyuki

• Noda, Kousuke

• Kawasaki, Akiko

• Yoshida, Shiho

• Dong, Yoko

• Saito, Michiyuki

• Dong, Zhenyu

• Ando, Ryo

• Mori, Shohei

• Saito, Wataru

• Kanda, Atsuhiro

• Ishida, Susumu

Bibliographic Information

Other Title

• Acrolein Production by VAP-1/SSAO

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.

Journal

• Current eye research

  Current eye research 42 (12), 1674-1683, 2017

  Taylor & Francis

Keywords

• Acrolein
• diabetic retinopathy
• hydrogen peroxide
• oxidative stress
• polyamine

Details

• CRID: 1050845763984850944
• NII Article ID: 120006540056
• DOI: 10.1080/02713683.2017.1359847
• ISSN: 14602202
• ISSN: 02713683
• HANDLE: 2115/72074
• Web Site: https://www.tandfonline.com/doi/pdf/10.1080/02713683.2017.1359847
• Text Lang: en
• Article Type: journal article
• Data Source:
  • IRDB
  • Crossref
  • CiNii Articles
  • KAKEN