Involvement of c-Jun NH2-terminal kinase-1 in heat-induced apoptotic cell death of human monoblastic leukaemia U937 cells

A. Enomoto, N. Suzuki, C. Liu, Y. Kang, J. Zhu, S. Serizawa, Y. Matsumoto, A. Morita, M. Ito, Y. Hosoi

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Purpose: To determine the involvement of c-Jun NH2-terminal kinase-1 (JNK1) and possibly of HSP27 in heat-induced apoptosis of human monoblastic leukaemia U937 cells. Materials and methods: Dominant negative JNK1 (APF), in which the phosphorylation sites Thr-Pro-Tyr were changed to Ala-Pro-Phe, was overexpressed in U937 cells. Cell viability and DNA fragmentation were analysed by the erythrosin-B dye exclusion test and by agarose gel electrophoresis, respectively. Expression of activated caspase-9, phosphorylated JNK1, JNK2, p38 and HSP27 was examined by Western blotting. JNK1 kinase assay was also performed using c-Jun as a substrate. Results: Loss of viability, activated cleavage form of caspase-9 and DNA fragmentation were rapid in U937 cells after 44°C hyperthermia, while overexpression of dominant negative JNK1 interfered with phosphorylation or activation of JNK1 without affecting that of JNK2 or p38/SAPK, and apparently delayed or reduced cleavage and activation of caspase-9, DNA fragmentation and cell death. Heat-induced phosphorylation of HSP27, observed in parental U937 cells, was suppressed and only slightly detectable in jnk1 mutant cells. Conclusions: Prolonged phosphorylation or activation of JNK1 was considered important for heat-induced apoptosis and JNK1 may control the process possibly through phosphorylation of HSP27 and caspase-9 activation in U937 cells.

Original languageEnglish
Pages (from-to)867-874
Number of pages8
JournalInternational Journal of Radiation Biology
Volume77
Issue number8
DOIs
Publication statusPublished - 2001 Sep 22
Externally publishedYes

ASJC Scopus subject areas

  • Radiological and Ultrasound Technology
  • Radiology Nuclear Medicine and imaging

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