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A Novel Prolyl Hydroxylase Inhibitor Protects Against Cell Death After Hypoxia

Content Provider	Springer Nature Link
Author	Kontani, Satoru Nagata, Eiichiro Uesugi, Tsuyoshi Moriya, Yusuke Fujii, Natsuko Miyata, Toshio Takizawa, Shunya
Copyright Year	2013
Abstract	Hypoxia-inducible factor 1 (HIF-1) is regulated by the oxygen-dependent hydroxylation of proline residues by prolyl hydroxylases (PHDs). We recently developed a novel PHD inhibitor, TM6008, that suppresses the activity of PHDs, inducing continuous HIF-1α activation. In this study, we investigated how TM6008 affects cell survival after hypoxic conditions capable of inducing HIF-1α expression and how TM6008 regulates PHDs and genes downstream of HIF-1α. After SHSY-5Y cells had been subjected to hypoxia, TM6008 was added to the cell culture medium under normoxic conditions. Apoptotic cell death was significantly augmented just after the hypoxic conditions, compared with cell death under normoxic conditions. Notably, when TM6008 was added to the media after the cells had been subjected to hypoxia, the expression level of HIF-1α increased and the number of cell deaths decreased, compared with the results for cells cultured in media without TM6008 after hypoxia, during the 7-day incubation period under normoxic conditions. Moreover, the protein expression levels of heme oxygenase 1, erythropoietin, and glucose transporter-3, which were genes downstream of HIF-1α, were elevated in media to which TM6008 had been added, compared with media without TM6008, during the 7-day incubation period under normoxic conditions. However, the protein expression levels of PHD2 and p53 which suppressed cell proliferation were suppressed in the media to which TM6008 had been added. Thus, TM6008, which suppresses the protein expressions of PHD2 and p53, might play an important role in cell survival after hypoxic conditions, with possible applications as a new compound for treatment after ischemic stroke.
Starting Page	2588
Ending Page	2594
Page Count	7
File Format	PDF
ISSN	03643190
Journal	Neurochemical Research
Volume Number	38
Issue Number	12
e-ISSN	15736903
Language	English
Publisher	Springer US
Publisher Date	2013-10-17
Publisher Place	Boston
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Prolyl hydroxylase inhibitor Hypoxia Hypoxia-inducible factor p53 Prolyl hydroxylase 2 Neurosciences Neurochemistry Biochemistry Cell Biology Neurology
Content Type	Text
Resource Type	Article
Subject	Medicine Biochemistry Cellular and Molecular Neuroscience

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A novel prolyl hydroxylase inhibitor protects against cell death after hypoxia.

A Novel Prolyl Hydroxylase Inhibitor Protects Against Cell Death After Hypoxia

Changes in Hypoxia-Inducible Factor-1 (HIF-1) and Regulatory Prolyl Hydroxylase (PHD) Enzymes Following Hypoxic–Ischemic Injury in the Neonatal Rat

Hypoxia Inducible Factor Prolyl 4-Hydroxylase Enzymes: Center Stage in the Battle Against Hypoxia, Metabolic Compromise and Oxidative Stress

ORIGINAL PAPER A Novel Prolyl Hydroxylase Inhibitor Protects Against Cell Death After Hypoxia

Hearts of Hypoxia-inducible Factor Prolyl 4-Hydroxylase-2 Hypomorphic Mice Show Protection against Acute Ischemia-Reperfusion Injury

Tight Control of Hypoxia-inducible Factor-α Transient Dynamics Is Essential for Cell Survival in Hypoxia

Notch Downregulation and Extramedullary Erythrocytosis in Hypoxia-Inducible Factor Prolyl 4-Hydroxylase 2-Deficient Mice.

Hypoxia-Inducible Factor Prolyl 4-Hydroxylase-2 Inhibition Protects Against Development of Atherosclerosis.

A Novel Prolyl Hydroxylase Inhibitor Protects Against Cell Death After Hypoxia

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A novel prolyl hydroxylase inhibitor protects against cell death after hypoxia.

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