Sodium orthovanadate suppresses DNA damage-induced caspase activation and apoptosis by inactivating p53

• MORITA Akinori

  Dept. Radiological Health, Grad. Sch. Med., Univ. Tokyo

• ENOMOTO Atsushi

  Dept. Radiat. Res., Grad. Sch. Med., Univ. Tokyo

• MATSUMOTO Yoshihisa

  Dept. Radiat. Res., Grad. Sch. Med., Univ. Tokyo

• SUZUKI Norio

  Dept. Radiat. Res., Grad. Sch. Med., Univ. Tokyo

• HOSOI Yoshio

  Dept. Radiat. Res., Grad. Sch. Med., Univ. Tokyo

Abstract

We previously reported that p42/SETß is a substrate for caspase-7 in irradiated MOLT-4 cells, and that treating the cells with sodium orthovanadate (vanadate, Na₃VO₄) inhibits p42/SETß's caspase-mediated cleavage. Here, we initially found that the inhibitory effect of vanadate was due to the suppression of caspase activation but not of caspase activity. Further investigations revealed that vanadate suppressed upstream of apoptotic events, such as the loss of mitochondrial membrane potential, the conformational change of Bax, and p53 transactivation, although the accumulation, total phosphorylation, and phosphorylation of six individual sites of p53 were not affected. Importantly, vanadate suppressed p53-dependent apoptosis, but not p53-independent apoptosis. Finally, gel-shift and chromatin immunoprecipitation (ChIP) assays conclusively demonstrated that vanadate inhibits the DNA-binding activity of p53. Vanadate is conventionally used as an inhibitor of protein tyrosine phosphatases (PTPs); however, we recommend that the influence of vanadate not only on PTPs but also on p53 be considered before using it.

Journal

• The Japan Radiation Research Society Annual Meeting Abstracts

  The Japan Radiation Research Society Annual Meeting Abstracts 2005 (0), 210-210, 2005

  The Japanese Radiation Research Society

Details

• CRID: 1390282680616371584
• NII Article ID: 130006999522
• DOI: 10.11513/jrrsabst.2005.0.210.0
• Text Lang: en
• Data Source:
  • JaLC
  • CiNii Articles
• Abstract License Flag: Disallowed