Level of HgCI2-mediated phosphorylation of intracellular proteins determines death of thymic T-lymphocytes with or without DNA fragmentation

Anwarul A. Akhand, Masashi Kato, Haruhiko Suzuki, Toshio Miyata, Izumi Nakashima

Research output: Contribution to journalArticlepeer-review

21 Citations (Scopus)

Abstract

Exposure to Hg2+ at a wide range of concentrations (approximately 1- 100 μM) more or less caused the death of murine thymic T-lymphocytes, and exposure to 1 μM but not 10 μM (or more) of Hg2+ induced DNA fragmentation. Exposure of cells to Hg2+ caused phosphorylation of multiple cellular proteins at the tyrosine residue in a concentration-dependent manner. We found that not only the DNA fragmentation induced by 1 μM Hg2+ but also the cell death bypassing DNA fragmentation caused by 10 μM or more Hg2+ was partly inhibited by protein kinase inhibitors such as staurosporine and herbimycin A. This result suggested the involvement of a protein phosphorylation-linked signal in the mechanism of the Hg2+-mediated cell death with or without DNA fragmentation. Analysis of proteins by both one- and two-dimensional electrophoresis and immunoblot showed that a 52-kDa Shc protein was heavily phosphorylated by an early signal delivered by a high concentration of Hg2+, which also phosphorylated extracellular signal- regulated kinase 1 (ERK1; p44) and ERK2 (p42) of the mitogen-activated protein kinase (MAPK) family in a concentration- and time-dependent manner. The c-Jun amino terminal kinase (p54), which is a distant relative of the MAPK family, was also phosphorylated by the treatment with Hg2+. This eventually formed the signaling cascade that ended with a nuclear target by phosphorylating c-jun at the serine 73. This phosphorylation of c-jun was inhibited by staurosporine. These results suggest that a high level of Hg2+-mediated protein phosphorylation-linked signal induces rapid cell death bypassing DNA fragmentation, whereas a lower level induces cell death accompanying DNA fragmentation. This conclusion in turn implies that DNA fragmentation is not always a prerequisite for the signal transduction- dependent cell death of T-lymphocytes.

Original languageEnglish
Pages (from-to)243-253
Number of pages11
JournalJournal of Cellular Biochemistry
Volume71
Issue number2
DOIs
Publication statusPublished - 1998 Nov 1
Externally publishedYes

Keywords

  • Apoptosis
  • HgCI
  • Signal transduction
  • T-lymphocyte
  • Tyrosine phosphorylation

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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