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Death and decoy receptors in neuronal preconditioning
Author(s) -
Panneerselvam Mathivadhani,
Patel Hemal H,
Head Brian P,
ChinLee Blake,
Patel Piyush M,
Davis Daniel P
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.716.11
Subject(s) - decoy , receptor , programmed cell death , in vivo , ischemia , tumor necrosis factor alpha , downregulation and upregulation , biology , pharmacology , microbiology and biotechnology , medicine , apoptosis , endocrinology , biochemistry , gene
Ischemic preconditioning (IPC) is a phenomenon where brief periods of ischemia confer protection against subsequent severe ischemic injury. The tumor necrosis factor (TNF) family of cytokines and receptors are involved in diverse signaling pathways regulating cell death and survival. Decoy receptors are a unique subset of these TNF receptors that can bind death ligands but do not contain cytoplasmic domains necessary to transduce signals. Therefore, decoy receptors serve to effectively compete for death ligands to promote cell survival. We hypothesized that decoy receptors may be upregulated after IPC to confer neuronal protection. Bilateral carotid occlusion in rats in vivo or oxygen‐glucose deprivation (OGD) in mixed cortical neurons from neonatal rats in vitro was used to induce neuronal death. IPC was induced by sublethal ischemia/OGD exposure (3 min in vivo or 20 min in vitro ) one day prior to lethal ischemia/OGD (6 min in vivo or 1 hr in vitro ). In the intact rat an increase in decoy molecule expression was observed in IPC versus controls in both CA1/3 and cortex. IPC induced increase in decoy expression was reduced by prior treatment with N‐methyl‐D‐aspartate receptor or nuclear factor‐kappa B inhibitors. Cell death and receptor expression was assessed 24–48 hrs after lethal ischemia in vitro . IPC resulted in reduced neuronal death when compared to controls. IPC followed by lethal ischemia resulted in altered regulation of decoy receptors and death receptors when compared to controls not undergoing IPC. Our results suggest that expression of decoy molecules and suppressed expression of death receptors may mediate neuronal survival induced by IPC.