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Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death
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Thymidine phosphorylase inhibits the expression of proapoptotic protein BNIP3

Ryuji Ikeda1, Yusuke Tajitsu, Ken-Ichi Iwashita

  • 1Department of Clinical Pharmacy and Pharmacology, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan.

Biochemical and Biophysical Research Communications
|March 25, 2008
PubMed

Insights

Thymidine phosphorylase (TP) and its product, 2-deoxy-d-ribose, prevent cell death from low oxygen. This occurs by suppressing the pro-apoptotic factor BNIP3, suggesting a role in tumor progression.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biochemistry

Background:

  • Angiogenic factors like thymidine phosphorylase (TP) are implicated in cancer.
  • TP is known to confer resistance to apoptosis, a key process in cell death.
  • Hypoxia (low oxygen) is a common condition in solid tumors that can induce apoptosis.

Purpose of the Study:

  • To elucidate the molecular mechanisms by which TP suppresses hypoxia-induced apoptosis.
  • To investigate the role of TP and its enzymatic product, 2-deoxy-d-ribose, in regulating apoptosis under hypoxic conditions.

Main Methods:

  • Utilized Jurkat cells stably transfected with TP cDNA (Jurkat/TP) and mock transfectants (Jurkat/CV).
  • Assessed apoptosis, expression of hypoxia-inducible factor 1alpha (HIF-1alpha), BNIP3, and caspase 3 activation under hypoxic conditions.
  • Employed small interfering RNA (siRNA) targeting BNIP3 to evaluate its role in hypoxia-induced apoptosis.

Main Results:

  • TP and 2-deoxy-d-ribose significantly suppressed hypoxia-induced apoptosis in Jurkat cells.
  • Both TP and 2-deoxy-d-ribose inhibited the hypoxia-induced upregulation of HIF-1alpha and BNIP3.
  • TP and 2-deoxy-d-ribose also inhibited hypoxia-induced caspase 3 activation.
  • Silencing BNIP3 expression using siRNA reduced the percentage of apoptotic cells under hypoxia.

Conclusions:

  • TP suppresses hypoxia-induced apoptosis, at least partly, by inhibiting BNIP3 expression.
  • The TP-generated product, 2-deoxy-d-ribose, contributes to this anti-apoptotic effect.
  • Elevated TP levels in solid tumors may promote tumor progression by preventing hypoxia-induced cell death via this mechanism.

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