Thymidine phosphorylase inhibits the expression of proapoptotic protein BNIP3
Section snippets
Materials and methods
Antibodies. The monoclonal anti-HIF-1α antibody was purchased from Transduction Laboratories (Lexington, KY). The monoclonal anti-actin (C-2) antibody was from Santa Cruz Biochemistry (Santa Cruz, CA) and monoclonal anti-BNIP3 (ab10433) were from Abcam Ltd. (Cambridge, UK).
Cell lines and induction of hypoxia. Human leukemia Jurkat cells and human colon cancer SW-620 cells were maintained in RPMI1640 containing 10% fetal calf serum. Hypoxia was induced with a Gas Pak Pouch Anaerobic System
The effect of TP on hypoxia-induced apoptosis in Jurkat cells
We examined the TP expression levels in Jurkat cells transfected with TP cDNA by immunoblotting using an anti-TP antibody. Jurkat/TP overexpressed TP, while Jurkat cells transfected with a control vector, Jurkat/CV, did not express a detectable amount of TP (Fig. 1A). We have previously shown that TP and 2-deoxy-d-ribose confer resistance to hypoxia-induced apoptosis on KB-3-1 cells [11]. To examine whether the similar effect of TP is observed in Jurkat cells, we measured hypoxia-induced
Discussion
Previous studies demonstrated that TP confers resistance to apoptosis induced by hypoxia and that the enzymatic activity of TP is required. 2-Deoxy-d-ribose, a degradation product of thymidine generated by TP activity can also prevent hypoxia-induced apoptosis in human KB epidermoid carcinoma cells [11] suggesting that it may be a downstream mediator of the TP function. 2-Deoxy-d-ribose prevented the hypoxia-induced activation of caspase 3 and 9 in HL-60 cells [12]. TP-overexpressing Jurkat/TP
References (30)
- et al.
Purification and properties of an endothelial cell growth factor from human platelets
J. Biol. Chem.
(1987) - et al.
The activity and expression of thymidine phosphorylase in human solid tumours
Eur. J. Cancer A
(1996) - et al.
Prevention of hypoxia-induced apoptosis by the angiogenic factor thymidine phosphorylase
Biochem. Biophys. Res. Commun.
(1998) - et al.
Molecular basis for the inhibition of hypoxia-induced apoptosis by 2-deoxy-d-ribose
Biochem. Biophys. Res. Commun.
(2002) - et al.
Up-regulation of apoptosis inhibitory protein IAP-2 by hypoxia. Hif-1-independent mechanisms
J. Biol. Chem.
(2001) - et al.
Nix and Nip3 form a subfamily of pro-apoptotic mitochondrial proteins
J. Biol. Chem.
(1999) - et al.
BNip3 and signal-specific programmed death in the heart
J. Mol. Cell. Cardiol.
(2005) - et al.
Kinetic studies of thymidine phosphorylase from mouse liver
Biochemistry
(1985) - et al.
Angiogenic factor
Nature
(1992) - et al.
Thymidine phosphorylase activity associated with platelet-derived endothelial cell growth factor
J. Biochem. (Tokyo)
(1993)
Angiogenic activity of enzymes
Nature
Identification of angiogenic activity and the cloning and expression of platelet-derived endothelial cell growth factor
Nature
Role of thymidine phosphorylase activity in the angiogenic effect of platelet derived endothelial cell growth factor/thymidine phosphorylase
Cancer Res.
Clinicopathologic and prognostic significance of an angiogenic factor, thymidine phosphorylase, in human colorectal carcinoma
J. Natl. Cancer Inst.
Expression of thymidine phosphorylase in human gastric carcinoma
Jpn. J. Cancer Res.
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Multifunctional role of thymidine phosphorylase in cancer
2022, Trends in CancerCitation Excerpt :Although TP is not a classical growth factor as it lacks a cell surface receptor [6], site-directed mutagenesis of active site residues and small molecule inhibitors have demonstrated that TP promotes angiogenesis via its catalytic activity [7,8]. The dephosphorylated product of thymidine catabolism, 2dDR, has chemotactic activity in vitro and angiogenic activity in vivo [7–10], and can confer resistance to hypoxia-induced apoptosis [11–14], glycate proteins altering their activity [15,16], and support alternate metabolic pathways [17,18]. These processes have the potential to sustain tumor growth and survival under nutrient deficient conditions and may underpin the aggressive and resilient nature of some cancers.
Activation of negative regulators of the hypoxia-inducible factor (HIF) pathway in human end-stage heart failure
2008, Biochemical and Biophysical Research CommunicationsAngiogenic growth factors in myocardial infarction: a critical appraisal
2017, Heart Failure ReviewsThymidine Phosphorylase in Cancer; Enemy or Friend?
2016, Cancer Microenvironment
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These authors contributed equally to this work.