Thymidine phosphorylase inhibits the expression of proapoptotic protein BNIP3 |
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Authors: | Ikeda Ryuji Tajitsu Yusuke Iwashita Ken-Ichi Che Xiao-Fang Yoshida Kenichi Ushiyama Mina Furukawa Tatsuhiko Komatsu Masaharu Yamaguchi Tatsuya Shibayama Yoshihiko Yamamoto Masatatsu Zhao Hong-Ye Arima Junko Takeda Yasuo Akiyama Shin-Ichi Yamada Katsushi |
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Affiliation: | a Department of Clinical Pharmacy and Pharmacology, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan b Department of Molecular Oncology, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan c Department of Environmental Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan d Department of Life Sciences, School of Agriculture, Meiji University, 1-1-1 Higashimita, Tama-ku, Kawasaki, Kanagawa 214-8571, Japan |
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Abstract: | An angiogenic factor, thymidine phosphorylase (TP), confers resistance to apoptosis induced by hypoxia. We investigated the molecular basis for the suppressive effect of TP on hypoxia-induced apoptosis using Jurkat cells transfected with TP cDNA, Jurkat/TP, and a mock transfectant, Jurkat/CV. TP and 2-deoxy-d-ribose, a degradation product of thymidine generated by TP enzymatic activity, suppressed hypoxia-induced apoptosis. They also inhibited the upregulation of hypoxia-inducible factor (HIF) 1α and the proapoptotic factor, BNIP3, and caspase 3 activation induced by hypoxia. Introduction of siRNA against BNIP3 in Jurkat cells decreased the proportion of apoptotic cells under hypoxic condition. These findings suggest that the suppression of BNIP3 expression by TP prevents, at least in part, hypoxia-induced apoptosis. Expression levels of TP are elevated in many malignant solid tumors and thus 2-deoxy-d-ribose generated by TP in these tumors might play an important role in tumor progression by preventing hypoxia-induced apoptosis. |
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Keywords: | Thymidine phosphorylase 2-Deoxy- smallcaps" >d-ribose Apoptosis Hypoxia-inducible factor-1α BNIP3 Hypoxia |
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