SNAP, a NO donor, induces cellular protection only when cortical neurons are submitted to some aggression process.
Nitric oxide is a versatile molecule, which plays important physiological and pathological roles. Its protective and toxic actions have been already evidenced in several cell types. However, the protective effect in cortical neurons remains elusive. In this work, we demonstrate that the NO-donor SNAP may induce both neuroprotection and neurotoxicity in this sort of cells. The protective effect of NO was evidenced when cortical neurons were exposed to deleterious conditions, such as serum deprivation. Serum deprivation induces apoptotic cortical neuron death through a caspase-dependent mechanism. Under these conditions, SNAP was able to oppose cell death through both caspase-3 inhibition and/or increase of antiapoptotic protein levels (Bcl-2 and Bcl-x(L)). On the other hand, in a normally serum-supplemented medium, high dose of SNAP behaves as a neurotoxic agent, through a mechanism which involves caspase-3 activation.
Figueroa
S
S
Instituto de Bioquímica (Centro Mixto CSIC-UCM), Facultad de Farmacia, Plaza Ramon y Cajal s/n Ciudad Universitaria, 28040-Madrid, Spain.
López
E
E
Arce
C
C
Oset-Gasque
M J
MJ
González
M P
MP
D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D053148:Caspase 3; D020169:Caspases / Q000187:drug effects / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D019610:Cytoprotection / Q000187:drug effects* / Q000502:physiology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009498:Neurotoxins / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D009573:Nitrites / Q000378:metabolism; D010396:Penicillamine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D051020:bcl-X Protein
C494813:Bcl2l1 protein, rat; D016895:Culture Media, Serum-Free; D018696:Neuroprotective Agents; D009498:Neurotoxins; D020030:Nitric Oxide Donors; D009573:Nitrites; D019253:Proto-Oncogene Proteins c-bcl-2; C110881:S-nitro-N-acetylpenicillamine; D051020:bcl-X Protein; D009569:Nitric Oxide; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases; D010396:Penicillamine