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Regulation of Spermine Oxidase through Hypoxia-Inducible Factor-1 alpha Signaling in Retinal Glial Cells under Hypoxic Conditions

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Title: Regulation of Spermine Oxidase through Hypoxia-Inducible Factor-1 alpha Signaling in Retinal Glial Cells under Hypoxic Conditions
Authors: Wu, Di Browse this author
Noda, Kousuke Browse this author →KAKEN DB
Murata, Miyuki Browse this author →KAKEN DB
Liu, Ye Browse this author
Kanda, Atsuhiro Browse this author →KAKEN DB
Ishida, Susumu Browse this author →KAKEN DB
Keywords: spermine oxidase
Muller glial cells
Issue Date: Jun-2020
Publisher: Association for Research in Vision and Ophthalmology(ARVO)
Journal Title: Investigative ophthalmology & visual science
Volume: 61
Issue: 6
Start Page: UNSP 52
Publisher DOI: 10.1167/iovs.61.6.52
Abstract: PURPOSE. Acrolein, a highly reactive unsaturated aldehyde, is known to facilitate glial cell migration, one of the pathological hallmarks in diabetic retinopathy. However, cellular mechanisms of acrolein generation in retinal glial cells remains elusive. In the present study, we investigated the role and regulation of spermine oxidase (SMOX), one of the enzymes related to acrolein generation, in retinal glial cells under hypoxic condition. METHODS. Immunofluorescence staining for SMOX was performed using sections of fibrovascular tissues obtained from patients with proliferative diabetic retinopathy. Expression levels of polyamine oxidation enzymes including SMOX were analyzed in rat retinal Muller cell line 5 (TR-MUL5) cells under either normoxic or hypoxic conditions. The transcriptional activity of Smox in TR-MUL5 cells was evaluated using the luciferase assay. Levels of acrolein-conjugated protein, N-epsilon-(3-formyl-3,4-dehydropiperidino) lysine adduct (FDP-Lys), and hydrogen peroxide were measured. RESULTS. SMOX was localized in glial cells in fibrovascular tissues. Hypoxia induced SMOX production in TR-MUL5 cells, which was suppressed by silencing of hypoxia-inducible factor-1 alpha (Hif1a), but not Hif2a. Transcriptional activity of Smox was regulated through HIF-1 binding to hypoxia response elements 2, 3, and 4 sites in the promoter region of Smox. Generation of FDP-Lys and hydrogen peroxide increased in TR-MUL5 cells under hypoxic condition, which was abrogated by SMOX inhibitor MDL72527. CONCLUSIONS. The current data demonstrated that hypoxia regulates production of SMOX, which plays a role in the generation of oxidative stress inducers, through HIF-1 alpha signaling in Muller glial cells under hypoxic condition.
Type: article
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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