Differential role for ERK2 in anoxia-induced activation of transcription and translation of Hsp70 in NIH 3T3 cells

Research output: Contribution to journalJournal articlepeer-review

  • Carlo Ossum
  • Anders N. Lauritsen
  • Dorina Gabriela Karottki
  • Else Kay Hoffmann
Hsp70 has the ability to enhance the recovery of stressed cells by its ability to catalyze the reassembly of damaged proteins. Such a chaperoning function is essential for the Hsp70-mediated protection against anoxic stress that causes protein denaturation. We have studied induction of both transcription and translation of Hsp70 during recovery from chemical anoxia and the role of the extracellular signal regulated kinase ERK2 in this induction of Hsp70. 10 mM azide for 30 minutes (chemical anoxia) significantly inhibited the activity of ERK2 (measured as phospho-ERK) but the ERK-2 activity is rapidly increased in a MEK-independen manner, when azide is washed out of the cells. Chemical anoxia and overnight recovery induced Hsp70 expression (analyzed by Western blotting) and this was inhibited by actinomycin D as well as by cycloheximide showing that induction of both translation and transcription was involved. Inhibition of the MAP kinase p38, which was transiently activated during chemical anoxia, had no effect on the increase in Hsp70 expression whereas an inhibitor of reactive oxygen species and inhibition of the phosphatase PP1 and PP2a inhibited the increase in Hsp70 expression. Inhibition of ERK2 by the MEK inhibitor PD98059 resulted in strong inhibition of Hsp70 protein expression and simultaneous stimulation of hsp70 transcription.
Original languageEnglish
JournalCellular Physiology and Biochemistry
Volume27
Issue number2
Pages (from-to)109-120
Number of pages12
ISSN1015-8987
DOIs
Publication statusPublished - 2011

    Research areas

  • Animals, Cell Hypoxia, Cycloheximide, Dactinomycin, Flavonoids, HSP70 Heat-Shock Proteins, Mice, Mitogen-Activated Protein Kinase 1, NIH 3T3 Cells, Protein Biosynthesis, Protein Phosphatase 1, Protein Phosphatase 2, Protein Synthesis Inhibitors, Reactive Oxygen Species, Sodium Azide, Transcriptional Activation, p38 Mitogen-Activated Protein Kinases

ID: 36070446