Sodium azide induced neuronal damage in vitro: evidence for non-apoptotic cell death.
The features of neuronal damage induced by the mitochondrial toxin NaN(3) were investigated in rat primary cortical neuron cultures. Cell viability (MTT colorimetric determination) and transmembrane mitochondrial potential (J-C1 fluorescence) were concentration-dependently reduced 24 h after NaN(3); neither nuclear fragmentation by DAPI, nor Annexin V positivity by flow cytometry were detected, ruling out the occurrence of apoptosis. The loss in cell viability (to 54 +/- 2%) observed 24 h after a 10-min treatment with 3 mM NaN(3) was prevented by the NMDA glutamate receptor antagonist MK801 (1 microM), by the antioxidants trolox (100 microM) and acetyl-L-carnitine (1 mM) and by the nitric oxide synthase inhibitor, L-NAME (100 microM), but not by the guanylylcyclase inhibitor ODQ, 10 microM. The mitochondrial dysfunction induced by NaN(3) provides a common platform for investigating the mechanisms of both ischemic and degenerative neuronal injury, useful for screening potential protective agents against neuronal death.
Dipartimento di Medicina Sperimentale e Diagnostica, Sezione di Genetica Medica, Università di Ferrara, Ferrara, Italy. svr@unife.it
Rita
R
Selvatici
Maurizio
M
Previati
Silvia
S
Marino
Luca
L
Marani
Sofia
S
Falzarano
Irene
I
Lanzoni
Anna
A
Siniscalchi
D000108:Acetylcarnitine / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis; D016923:Cell Death / Q000187:drug effects; D002467:Cell Nucleus / Q000187:drug effects / Q000648:ultrastructure; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D002839:Chromans / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors; D053078:Membrane Potential, Mitochondrial; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010069:Oxadiazoles / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D019810:Sodium Azide / Q000633:toxicity*
C095284:1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; D000975:Antioxidants; D002839:Chromans; D018696:Neuroprotective Agents; D010069:Oxadiazoles; D011810:Quinoxalines; D016194:Receptors, N-Methyl-D-Aspartate; D000108:Acetylcarnitine; D016291:Dizocilpine Maleate; D019810:Sodium Azide; D019001:Nitric Oxide Synthase; D006162:Guanylate Cyclase; C010643:6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid; D019331:NG-Nitroarginine Methyl Ester