Heat-shock protein 27 (Hsp27) as a target of methylglyoxal in gastrointestinal cancer

  • T. O
  • Y. N
  • T. T
  • et al.
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Abstract

The molecular mechanisms underlying the posttranslational modification of proteins in gastrointestinal cancer are still unknown. Here, we investigated the role of methylglyoxal modifications in gastrointestinal tumors. Methylglyoxal is a reactive dicarbonyl compound produced from cellular glycolytic intermediates that reacts non-enzymatically with proteins. By using a monoclonal antibody to methylglyoxal-modified proteins, we found that murine heat-shock protein 25 and human heat-shock protein 27 were the major adducted proteins in rat gastric carcinoma mucosal cell line and human colon cancer cell line, respectively. Furthermore, we found that heat-shock protein 27 was modified by methylglyoxal in ascending colon and rectum of patients with cancer. However, methylglyoxal-modified heat-shock protein 25/heat-shock protein 27 was not detected in non cancerous cell lines or in normal subject. Matrix-associated laser desorption/ionization mass spectrometry/mass spectrometry analysis of peptide fragments identified Arg-75, Arg-79, Arg-89, Arg-94, Arg-127, Arg-136, Arg-140, Arg-188, and Lys-123 as methylglyoxal modification sites in heat-shock protein 27 and in phosphorylated heat-shock protein 27. The transfer of methylglyoxal-modified heat-shock protein 27 into rat intestinal epithelial cell line RIE was even more effective in preventing apoptotic cell death than that of native control heat-shock protein 27. Furthermore, methylglyoxal modification of heat-shock protein 27 protected the cells against both the hydrogen peroxide- and cytochrome c-mediated caspase activation, and the hydrogen peroxide-induced production of intracellular reactive oxygen species. The levels of lactate converted from methylglyoxal were increased in carcinoma mucosal cell lines. Our results suggest that posttranslational modification of heat-shock protein 27 by methylglyoxal may have important implications for epithelial cell injury in gastrointestinal cancer. © 2011 Elsevier B.V.

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T., O.-I. T., Y., N., T., T., O., H., H., M., M., Y., … T., Y. (2011). Heat-shock protein 27 (Hsp27) as a target of methylglyoxal in gastrointestinal cancer. Biochimica et Biophysica Acta - Molecular Basis of Disease. T. Oya-Ito, Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kaji-i, Kyoto 602-8566, Japan. E-mail: oya-ito@koto.kpu-m.ac.jp: Elsevier (P.O. Box 211, Amsterdam 1000 AE, Netherlands). Retrieved from http://ovidsp.ovid.com/ovidweb.cgi?T=JS&PAGE=reference&D=emed10&NEWS=N&AN=2011247894

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