Thymidine phosphorylase inhibits the expression of proapoptotic protein BNIP3

• Published in: Biochemical and biophysical research communications Vol. 370; no. 2; pp. 220 - 224
• Main 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
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 30-05-2008
• Subjects: 2-Deoxy-d-ribose; Apoptosis; Apoptosis - drug effects; Apoptosis - genetics; BNIP3; Caspase 3 - metabolism; Caspase 8 - metabolism; Cell Hypoxia - genetics; Deoxyribose - metabolism; Humans; Hypoxia; Hypoxia-Inducible Factor 1, alpha Subunit - metabolism; Hypoxia-inducible factor-1α; Jurkat Cells; Membrane Proteins - antagonists & inhibitors; Membrane Proteins - genetics; Proto-Oncogene Proteins - antagonists & inhibitors; Proto-Oncogene Proteins - genetics; RNA, Small Interfering - genetics; RNA, Small Interfering - pharmacology; Thymidine phosphorylase; Thymidine Phosphorylase - genetics; Thymidine Phosphorylase - metabolism; Transfection; Hypoxia-inducible factor-1α; Hypoxia; 2-Deoxy-d-ribose; BNIP3; Thymidine phosphorylase; Apoptosis
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2008.03.067

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.