Retinoic acid reduces apoptosis and oxidative stress by preservation of SOD protein level.
Retinoic acid (RA) has already been shown to exert antiapoptotic and antioxidative activity in various cells. In this study, we determined the effect of RA on the mRNA and protein levels of the Cu-,Zn-superoxide dismutase (SOD-1) and Mn-superoxide dismutase (SOD-2) during staurosporine-induced apoptosis in primary cultures from neonatal rat hippocampus. Exposure to staurosporine (300 nM, 24 h) increased the percentage of apoptotic neurons to 62% compared with 18% in controls. We determined an increase in the reactive oxygen species (ROS) content from 4 up to 48 h after the induction of the injury. Treatment with staurosporine did not significantly change the mRNA levels of SOD-1 and SOD-2. However, the SOD-1 and SOD-2 protein levels markedly decreased 24 and 48 h after the addition of staurosporine. Compared with staurosporine-exposed controls, RA (10 nM)-treated cultures showed a significant increase in neuronal survival, a reduced neuronal ROS content, and enhanced protein levels of SOD-1 and SOD-2 24 and 48 h after the start of the exposure to staurosporine. The results suggest that RA reduced staurosporine-induced oxidative stress and apoptosis by preventing the decrease in the protein levels of SOD-1 and SOD-2, and thus supported the antioxidant defense system.
Ahlemeyer
B
B
Institut für Pharmakologie und Toxikologie, Fachbereich Pharmazie der Philipps-Universität Marburg, Marburg, Germany. ahlemeye@mailer.uni-marburg.de
Bauerbach
E
E
Plath
M
M
Steuber
M
M
Heers
C
C
Tegtmeier
F
F
Krieglstein
J
J
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002478:Cells, Cultured; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D008856:Microscopy, Fluorescence; D009474:Neurons / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D017382:Reactive Oxygen Species / Q000378:metabolism; D019311:Staurosporine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism*; D000072105:Superoxide Dismutase-1; D014212:Tretinoin / Q000494:pharmacology*; D000099156:Superoxide Dismutase 2
D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D019311:Staurosporine; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D014212:Tretinoin; D000099156:Superoxide Dismutase 2; C000606292:Sod1 protein, rat