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Title: Phosphorylation of p53 at serine 15 in A549 pulmonary epithelial cells exposed to vanadate: Involvement of ATM pathway

Abstract

When A549 cells were exposed to sodium metavanadate (NaVO{sub 3}), the pentavalent species of vanadium (vanadate), phosphorylation of p53 protein at Ser15 was found in a time (8-48 h)- and dose (10-200 {mu}M)-dependent manner. After the incubation with 50 or 100 {mu}M NaVO{sub 3} for 48 h, accumulation of p53 protein was accompanied with Ser15 phosphorylation. Among serines in p53 protein immunoprecipitated from A549 cells treated with 100 {mu}M NaVO{sub 3} for 48 h, only Ser15 was markedly phosphorylated. Treatment with other vanadate compounds, sodium orthovanadate (Na{sub 3}VO{sub 4}) and ammonium metavanadate (NH{sub 4}VO{sub 3}), also induced Ser15 phosphorylation and accumulation of p53 protein. While phosphorylation of extracellular signal-regulated protein kinase (ERK) was found in cells treated with NaVO{sub 3}, treatment with U0126 did not suppress Ser15 phosphorylation. On the other hand, treatment with wortmannin or caffeine, the inhibitors to phosphatidylinositol 3-kinase related kinases (PIKKs), suppressed both NaVO{sub 3}-induced Ser15 phosphorylation and accumulation of p53 protein. The silencing of ataxia telangiectasia mutated (ATM) expression using short-interference RNA resulted in the marked suppression of Ser15 phosphorylation in A549 cells exposed to NaVO{sub 3}. However, treatment with antioxidants such as catalase and N-acetylcysteine did not suppress NaVO{sub 3}-induced Ser15 phosphorylation. Transcriptional activationmore » of p53 and DNA fragmentation in A549 cells treated with NaVO{sub 3} were suppressed only slightly by S15A mutation, suggesting that Ser15 phosphorylation is not essential for these responses. The present results showed that vanadate induces the phosphorylation of p53 at Ser15 depending on ATM, one of the members of PIKK family, in this human pulmonary epithelial cell line.« less

Authors:
 [1];  [1];  [1];  [2]
  1. Department of Hygiene and Public Health I, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666 (Japan)
  2. Department of Hygiene and Public Health I, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666 (Japan). E-mail: matsuoka@research.twmu.ac.jp
Publication Date:
OSTI Identifier:
20976900
Resource Type:
Journal Article
Resource Relation:
Journal Name: Toxicology and Applied Pharmacology; Journal Volume: 220; Journal Issue: 1; Other Information: DOI: 10.1016/j.taap.2006.12.028; PII: S0041-008X(06)00509-6; Copyright (c) 2007 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ANTIOXIDANTS; CAFFEINE; CATALASE; DMSO; DNA; INHIBITION; MUTATIONS; PHOSPHORYLATION; PHOSPHOTRANSFERASES; POLYMERASE CHAIN REACTION; RNA; SERINE; SODIUM; STRAND BREAKS; VANADATES; VANADIUM

Citation Formats

Suzuki, Katsura, Inageda, Kiyoshi, Nishitai, Gen, and Matsuoka, Masato. Phosphorylation of p53 at serine 15 in A549 pulmonary epithelial cells exposed to vanadate: Involvement of ATM pathway. United States: N. p., 2007. Web. doi:10.1016/j.taap.2006.12.028.
Suzuki, Katsura, Inageda, Kiyoshi, Nishitai, Gen, & Matsuoka, Masato. Phosphorylation of p53 at serine 15 in A549 pulmonary epithelial cells exposed to vanadate: Involvement of ATM pathway. United States. doi:10.1016/j.taap.2006.12.028.
Suzuki, Katsura, Inageda, Kiyoshi, Nishitai, Gen, and Matsuoka, Masato. Sun . "Phosphorylation of p53 at serine 15 in A549 pulmonary epithelial cells exposed to vanadate: Involvement of ATM pathway". United States. doi:10.1016/j.taap.2006.12.028.
@article{osti_20976900,
title = {Phosphorylation of p53 at serine 15 in A549 pulmonary epithelial cells exposed to vanadate: Involvement of ATM pathway},
author = {Suzuki, Katsura and Inageda, Kiyoshi and Nishitai, Gen and Matsuoka, Masato},
abstractNote = {When A549 cells were exposed to sodium metavanadate (NaVO{sub 3}), the pentavalent species of vanadium (vanadate), phosphorylation of p53 protein at Ser15 was found in a time (8-48 h)- and dose (10-200 {mu}M)-dependent manner. After the incubation with 50 or 100 {mu}M NaVO{sub 3} for 48 h, accumulation of p53 protein was accompanied with Ser15 phosphorylation. Among serines in p53 protein immunoprecipitated from A549 cells treated with 100 {mu}M NaVO{sub 3} for 48 h, only Ser15 was markedly phosphorylated. Treatment with other vanadate compounds, sodium orthovanadate (Na{sub 3}VO{sub 4}) and ammonium metavanadate (NH{sub 4}VO{sub 3}), also induced Ser15 phosphorylation and accumulation of p53 protein. While phosphorylation of extracellular signal-regulated protein kinase (ERK) was found in cells treated with NaVO{sub 3}, treatment with U0126 did not suppress Ser15 phosphorylation. On the other hand, treatment with wortmannin or caffeine, the inhibitors to phosphatidylinositol 3-kinase related kinases (PIKKs), suppressed both NaVO{sub 3}-induced Ser15 phosphorylation and accumulation of p53 protein. The silencing of ataxia telangiectasia mutated (ATM) expression using short-interference RNA resulted in the marked suppression of Ser15 phosphorylation in A549 cells exposed to NaVO{sub 3}. However, treatment with antioxidants such as catalase and N-acetylcysteine did not suppress NaVO{sub 3}-induced Ser15 phosphorylation. Transcriptional activation of p53 and DNA fragmentation in A549 cells treated with NaVO{sub 3} were suppressed only slightly by S15A mutation, suggesting that Ser15 phosphorylation is not essential for these responses. The present results showed that vanadate induces the phosphorylation of p53 at Ser15 depending on ATM, one of the members of PIKK family, in this human pulmonary epithelial cell line.},
doi = {10.1016/j.taap.2006.12.028},
journal = {Toxicology and Applied Pharmacology},
number = 1,
volume = 220,
place = {United States},
year = {Sun Apr 01 00:00:00 EDT 2007},
month = {Sun Apr 01 00:00:00 EDT 2007}
}