TY - JOUR
T1 - Selective potentiation of NMDA-induced neuronal injury following induction of astrocytic iNOS
AU - Hewett, Sandra I.
AU - Csernansky, Cynthia A.
AU - Choi, Dennis W.
N1 - Funding Information:
The authors would liketo thank Susan Adams and Lisa Feldhaus for technical assistance. In addition, helpful discussions with Dts. John Cotbett, Michael McDaniel, and Laura Dugan ate gratefully acknowledged. This work was supported by NIH grants NS 30337 (D. W. C.), NS 07027 (S. 1. H.), and DA 07261 (C. A. C.).
PY - 1994/8
Y1 - 1994/8
N2 - Nitric oxide (NO) produced by the constitutive NO synthase (cNOS) in neurons has been implicated in mediating excitotoxic neuronal death. In our murine cortical cell culture system, NMDA neurotoxicity was not blocked by addition of the NOS inhibitors, NG-nitrol-arginine or aminoguanidine. However, following activation of inducible NOS in astrocytes by interleukin-1 β plus interferon-γ, NMDA but not kainate neurotoxicity was markedly potentiated. This selective potentiation of NMDA neurotoxicity was blocked by NOS inhibition or antioxidants (superoxide dismutase/catalase or Tempol) and could be mimicked by NO generators (SIN-1 or SNAP) or the oxygen radical generator, pyragallol. These results raise the possibility that NO production by astrocytes may contribute to NMDA receptor-mediated neuronal death, perhaps through interaction with oxygen radicals.
AB - Nitric oxide (NO) produced by the constitutive NO synthase (cNOS) in neurons has been implicated in mediating excitotoxic neuronal death. In our murine cortical cell culture system, NMDA neurotoxicity was not blocked by addition of the NOS inhibitors, NG-nitrol-arginine or aminoguanidine. However, following activation of inducible NOS in astrocytes by interleukin-1 β plus interferon-γ, NMDA but not kainate neurotoxicity was markedly potentiated. This selective potentiation of NMDA neurotoxicity was blocked by NOS inhibition or antioxidants (superoxide dismutase/catalase or Tempol) and could be mimicked by NO generators (SIN-1 or SNAP) or the oxygen radical generator, pyragallol. These results raise the possibility that NO production by astrocytes may contribute to NMDA receptor-mediated neuronal death, perhaps through interaction with oxygen radicals.
UR - http://www.scopus.com/inward/record.url?scp=0027932457&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0027932457&partnerID=8YFLogxK
U2 - 10.1016/0896-6273(94)90362-X
DO - 10.1016/0896-6273(94)90362-X
M3 - Article
C2 - 7520256
AN - SCOPUS:0027932457
SN - 0896-6273
VL - 13
SP - 487
EP - 494
JO - Neuron
JF - Neuron
IS - 2
ER -