en
Scientific article
English

Control of death receptor and mitochondrial-dependent apoptosis by c-Jun N-terminal kinase in hippocampal CA1 neurones following global transient ischaemia

Published inJournal of neurochemistry, vol. 92, no. 5, p. 1054-1060
Publication date2005
Abstract

c-Jun N-terminal kinase (JNK), a member of the mitogen-activated protein kinase family, is activated in response to a number of extracellular stimuli, including inflammatory cytokines, UV irradiation and ischaemia. A large body of evidence supports a role for JNK signalling in stress-induced apoptosis. It has been hypothesized that JNK may contribute to the apoptotic response by regulating the intrinsic cell death pathway involving the mitochondria. Here, we examined the role of the JNK signalling pathway in hippocampal CA1 apoptotic neurones following transient ischaemia in gerbils. We showed early activation of death receptor-dependent apoptosis (caspase-8 activation 2 days after ischaemia) and a biphasic activation of caspase-3 and caspase-9 after ischaemia. Activation of the mitochondrial pathway, as measured by cytochrome c release, appeared as a late event (5-7 days after ischaemia). AS601245, a novel JNK inhibitor, antagonized activation of both pathways and significantly protected CA1 neurones from cell death. Our results suggest a key role of JNK in the control of death receptor and mitochondrial-dependent apoptosis after transient ischaemia.

Keywords
  • Acetonitriles/pharmacology/therapeutic use
  • Analysis of Variance
  • Animals
  • Apoptosis
  • Benzothiazoles
  • Caspases/classification/metabolism
  • Cytochromes c/metabolism
  • Enzyme Activation/drug effects
  • Gerbillinae
  • Hippocampus/pathology
  • In Situ Nick-End Labeling/methods
  • Ischemic Attack, Transient/drug therapy/enzymology/pathology
  • JNK Mitogen-Activated Protein Kinases/antagonists & inhibitors/physiology
  • Male
  • Mitochondria/drug effects/metabolism
  • Neurons/drug effects/metabolism
  • Reperfusion Injury/prevention & control
  • Thiazoles/pharmacology/therapeutic use
  • Time Factors
Affiliation Not a UNIGE publication
Citation (ISO format)
CARBONI, Sonia et al. Control of death receptor and mitochondrial-dependent apoptosis by c-Jun N-terminal kinase in hippocampal CA1 neurones following global transient ischaemia. In: Journal of neurochemistry, 2005, vol. 92, n° 5, p. 1054–1060. doi: 10.1111/j.1471-4159.2004.02925.x
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Article (Published version)
accessLevelRestricted
Identifiers
ISSN of the journal0022-3042
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