We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
GluR6-FasL-Trx2 mediates denitrosylation and activation of procaspase-3 in cerebral ischemia/reperfusion in rats.
- Authors
N. Sun; J-R. Hao; X-Y. Li; X-H. Yin; Y-Y. Zong; G-Y. Zhang; C. Gao
- Abstract
Global cerebral ischemia/reperfusion (I/R) facilitates the activation of procaspase-3 and promotes apoptosis in hippocampus. But the mechanisms have remained uncharacterized. Protein S-nitrosylation and denitrosylation is an important reversible posttranslational modification, which is a common mechanism in signal transduction and affects numerous physiological and pathophysiological events. However, it is not known whether S-nitrosylation/denitrosylation modification of procaspase-3 serves as a component of apoptosis and cell death induced by cerebral I/R. Here we show that procaspase-3 is significantly denitrosylated and activated after I/R in rat hippocampus. NS102, a glutamate receptor 6 (GluR6) antagonist, can inhibit the denitrosylation of procaspase-3 and diminish the increased Fas ligand (FasL) and thioredoxin (Trx)-2 expression induced by cerebral I/R. Moreover, downregulation of FasL expression by antisense oligodeoxynucleotides inhibits the denitrosylation and activation of procaspase-3. Auranofin, a TrxR inhibitor or TrxR2 antisense oligodeoxynucleotide, has similar effects. In primary hippocampal cultures, Lentiviral-mediated knockdown of FasL and TrxR2 before the oxygen and glucose deprivation/reoxygenation further verifies that FasL and TrxR2 are involved in the denitrosylation of procaspase-3. In situ TUNEL staining and cresyl violet staining validate that inhibiting denitrosylation of procaspase-3 may exert neuroprotective effect on apoptosis and cell death induced by cerebral I/R in hippocampal CA1 pyramidal neurons. This is the first evidence that cerebral I/R mediates procaspase-3 denitrosylation and activation through GluR6-FasL-Trx2 pathway, which leads to neuronal apoptosis and cell death
- Publication
Cell Death & Disease, 2013, Vol 4, Issue 8, p1
- ISSN
2041-4889
- Publication type
Article
- DOI
10.1038/cddis.2013.299