Molecular basis for the regulation of hypoxia-inducible factor-1α levels by 2-deoxy-D-ribose

Ikeda,Ryuji; Tabata,Sho; Tajitsu,Yusuke; Nishizawa,Yukihiko; Minami,Kentaro; Furukawa,Tatsuhiko; Yamamoto,Masatatsu; Shinsato,Yoshinari; Akiyama,Shin-Ichi; Yamada,Katsushi; Takeda,Yasuo

doi:10.3892/or.2013.2572

Molecular basis for the regulation of hypoxia-inducible factor-1α levels by 2-deoxy-D-ribose

Authors:
- Ryuji Ikeda
- Sho Tabata
- Yusuke Tajitsu
- Yukihiko Nishizawa
- Kentaro Minami
- Tatsuhiko Furukawa
- Masatatsu Yamamoto
- Yoshinari Shinsato
- Shin-Ichi Akiyama
- Katsushi Yamada
- Yasuo Takeda
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Affiliations: Department of Clinical Pharmacy and Pharmacology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-852, Japan, Department of Respiratory Medicine and Rheumatology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima 770-8503, Japan, Department of Molecular Oncology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-852, Japan, Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Nagasaki International University, Nagasaki 859-3298, Japan
Published online on: June 27, 2013 https://doi.org/10.3892/or.2013.2572
Pages: 1444-1448

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Abstract

The angiogenic factor, platelet-derived endothelial cell growth factor/thymidine phosphorylase (PD-ECGF/TP), stimulates the chemotaxis of endothelial cells and confers resistance to apoptosis induced by hypoxia. 2-Deoxy-D-ribose, a degradation product of thymidine generated by TP enzymatic activity, inhibits the upregulation of hypoxia-inducible factor (HIF) 1α, BNIP3 and caspase-3 induced by hypoxia. In the present study, we investigated the molecular basis for the suppressive effect of 2-deoxy-D-ribose on the upregulation of HIF-1α. 2-Deoxy-D-ribose enhanced the interaction of HIF-1α and the von Hippel-Lindau (VHL) protein under hypoxic conditions. It did not affect the expression of HIF-1α, prolyl hydroxylase (PHD)1/2/3 and VHL mRNA under normoxic or hypoxic conditions, but enhanced the interaction of HIF-1α and PHD2 under hypoxic conditions. 2-Deoxy-D-ribose also increased the amount of hydroxy-HIF-1α in the presence of the proteasome inhibitor MG-132. The expression levels of TP are elevated in many types of malignant solid tumors and, thus, 2-deoxy-D-ribose generated by TP in these tumors may play an important role in tumor progression by preventing hypoxia-induced apoptosis.

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