Retinoic acid reduces staurosporine-induced apoptotic damage in chick embryonic neurons by suppressing reactive oxygen species production.
The effect of all-trans retinoic acid (RA), which is known as a regulator of cell growth and differentiation, was studied during neuronal apoptosis. Apoptosis was induced in primary cultures of chick embryonic neurons by treatment with staurosporine (200 nM) for 24 h which led to a reduction of cellular viability to 40% compared to 83% in untreated cultures as well as to an increase in the number of apoptotic neurons (determined by nuclear staining with Hoechst 33258) to 60% compared to 15% in untreated cultures. RA (1 nM-10 microM) reduced the number of non-viable and apoptotic cells in a concentration-dependent manner and the maximal response was seen at 1 microM RA with 60% cellular viability and 38% apoptotic neurons. The production of mitochondrial reactive oxygen species (ROS, determined by the fluorescent indicator dihydrorhodamine) was elevated 4.4-fold after 4 h of staurosporine-treatment which was reduced to a 2-fold increase in the presence of 10 microM RA. The results indicate that RA was able to reduce apoptotic damage in staurosporine-treated chick embryonic neurons by suppressing the production of ROS.
Ahlemeyer
B
B
Institut für Pharmakologie und Toxikologie, Fachbereich Pharmazie der Philipps-Universität Marburg, Germany. ahlemeye@mailer.uni-marburg.de
Krieglstein
J
J
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D006690:Bisbenzimidazole; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002642:Chick Embryo; D002843:Chromatin / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D004305:Dose-Response Relationship, Drug; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism*; D019311:Staurosporine / Q000494:pharmacology*; D014212:Tretinoin / Q000494:pharmacology*
D002843:Chromatin; D017382:Reactive Oxygen Species; D014212:Tretinoin; D019311:Staurosporine; D006690:Bisbenzimidazole