Open AccessFyn Kinases Play a Critical Role in Neuronal Apoptosis Induced by Oxygen and Glucose Deprivation or Amyloid‐β Peptide Treatment
Author(s) -
Du CaiPing,
Tan Ran,
Hou XiaoYu
Publication year - 2012
Publication title -
cns neuroscience and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 69
eISSN - 1755-5949
pISSN - 1755-5930
DOI - 10.1111/j.1755-5949.2012.00357.x
Subject(s) - gene knockdown , phosphorylation , neuroprotection , kinase , excitotoxicity , microbiology and biotechnology , tyrosine phosphorylation , biology , apoptosis , chemistry , pharmacology , biochemistry , programmed cell death
Summary Aims S rc family protein tyrosine kinases ( S rc PTK s) have been implicated in the pathogenesis of brain ischemia and A lzheimer's disease ( AD ). In this study, we investigated whether S rc and F yn kinases, two major members of S rc PTK s in the brain, have distinct roles in the oxygen and glucose deprivation ( OGD ) and amyloid‐β peptide ( A β)‐induced neuronal apoptosis. Methods and results The DAPI staining and caspase‐3 activation analysis showed that small interfering RNA s (si RNA s) knockdown of S rc or F yn attenuated SH ‐ SY 5 Y cells apoptosis after OGD and A β treatment. F yn knockdown had a more potent neuroprotective effect than S rc knockdown, suggesting a principal pathological significance of F yn in brain ischemia and AD . Previously, we reported that brain ischemia promotes the phosphorylation of postsynaptic density protein 95 ( PSD ‐95) at tyrosine 523 ( Y 523), which is associated with postsynaptic mechanisms of excitotoxicity. Here, immunoblot analysis indicated that not only OGD but also A β incubation increased the PSD ‐95 Y 523 phosphorylation. S rc knockdown, especially F yn knockdown, significantly inhibited such phosphorylation. Conclusion F yn mediates PSD ‐95Y523 phosphorylation, which may be responsible for the excitotoxic signal cascades and neuronal apoptosis in brain ischemia and A β neurotoxicity. F yn is a potential therapeutic target for the treatment of ischemic stroke and AD .