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Caspase inhibition by cardiotrophin‐1 prevents neuronal death in vivo and in vitro
Author(s) -
Peng Hui,
Sola Augusto,
Moore James,
Wen Tongchun
Publication year - 2010
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.22269
Subject(s) - in vivo , mapk/erk pathway , kinase , microbiology and biotechnology , medicine , biology , pharmacology
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. © 2009 Wiley‐Liss, Inc.