Caspase inhibition by cardiotrophin-1 prevents neuronal death in vivo and in vitro

Hui Peng, Augusto Sola, James Moore, Tongchun Wen

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

Our previous studies showed that cardiotrophin-1 (CT-1), a cytokine in the interleukin-6 family, protected the developing rat brain against focal cerebral ischemia (FCI) in vivo and prevented cortical neuron death in vitro. However, the mechanisms by which CT-1 prevents neuronal death are not clearly understood. This in vivo study focused on whether CT-1 treatment prevented FCI-induced brain injuries in the postnatal day 7 (P7) rat through modulating activation of the initiator caspase-8 (C-8) and the downstream effector caspase-3 (C-3). FCI caused a significant increase in expressions of cleaved C-8 and C-3 and, meanwhile, a significant decrease in expression of microtubule-associated protein-2 (MAP2) in the left ischemic cortex of the P7 rat brain after FCI. Exogenous treatment of CT-1 significantly reduced the expression of cleaved C-8 or C-3 and attenuated the decline in MAP2 expression in the ischemic cortex from 12 to 24 hr after FCI. Subsequent in vitro experiments demonstrated that CT-1 treatment inhibited sodium nitroprusside (SNP)-induced activation of C-8 and C-3 and loss of MAP2-positive neurons in cortical neuron cultures. More importantly, CT-1 activated several pathways, including Janus kinase 2, signal transducers and activators of transcription 3, nuclear factor kappa B, mitogen-activated protein kinase (MAPK), and MAPK kinase in the cultures exposed to SNP. This is the first suggestion that CT-1 prevents neuronal injury in the developing central nervous system possibly through mediating multiple signal pathways, inhibiting activation of C-8 and C-3.

Original languageEnglish (US)
Pages (from-to)1041-1051
Number of pages11
JournalJournal of Neuroscience Research
Volume88
Issue number5
DOIs
StatePublished - Apr 1 2010

Keywords

  • Apoptosis
  • Caspases
  • Focal cerebral ischemia
  • Neonatal rats
  • Signal pathways

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

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