Reactive species and apoptosis of neural precursor cells after gamma-irradiation.
This study addresses the participation of radiation-induced free radicals, mainly nitric oxide (NO), in modulating the apoptotic response in an in vitro model of neural cortical precursor cells exposed to gamma-radiation. Cortical cells obtained from rats at 17 gestational day (GD) were irradiated with a dose of 2 Gy. The percentage of apoptotic cells was significantly increased 4h post-irradiation (pi). NO content showed a significant increase after 30 min pi and the rate of generation reached a maximum 1h pi. Luminol-dependent chemiluminescence (CL) was significantly higher in cells after 2h pi as compared to control cells and this profile was maintained up to 4 h pi. Supplementation with L-NAME significantly increased light emission. Administration of superoxide dismutase (SOD) following L-NAME addition prevented the observed changes due to L-NAME administration. The caspase inhibitor zDEVD-fmk significantly reduced the radical generation. Moreover, the cellular decrease in NO content occurred coincidentally with the rise in oxygen radical generation and the activation of caspase-3. In vitro irradiation of neural precursor cells allowed us to suggest that an early radiation-induced generation of NO could exert a neuroprotective role. However, despite this NO initial protective effect and its role modulating the response against gamma-radiation, NO generation was not able of fully preventing radiation-induced apoptosis.
Gisone
Pablo
P
Nuclear Regulatory Authority, Radiopathology Laboratory, Avenida del Libertador 8250 (C1429BNP) Buenos Aires, Argentina.
Robello
Elizabeth
E
Sanjurjo
Julieta
J
Dubner
Diana
D
Pérez
María del Rosario
Mdel R
Michelin
Severino
S
Puntarulo
Susana
S
D000818:Animals; D017209:Apoptosis / Q000528:radiation effects*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005434:Flow Cytometry; D005720:Gamma Rays; D008163:Luminescent Measurements; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009474:Neurons / Q000528:radiation effects*; D009566:Nitrates / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I / Q000037:antagonists & inhibitors; D009573:Nitrites / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013234:Stem Cells / Q000528:radiation effects*; D013481:Superoxides / Q000378:metabolism
D004791:Enzyme Inhibitors; D009566:Nitrates; D009573:Nitrites; D017382:Reactive Oxygen Species; D013481:Superoxides; D009569:Nitric Oxide; D052248:Nitric Oxide Synthase Type I; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases; D019331:NG-Nitroarginine Methyl Ester