Hypoxia-induced Cell Death and Activation of Pro- and Anti-apoptotic Proteins in Developing Chick Optic Lobe
Exposure of the CNS to hypoxia is associated with cell death. Our aim was to establish a temporal correlation between cellular and molecular alterations induced by an acute hypoxia evaluated at different post-hypoxia (p-h) times and at two stages of chick optic lobe development: embryonic days (ED) 12 and 18. TUNEL assays at ED12 disclosed a significant increase (300%) in pyknotic cells at 6 h p-h, while at ED18 no morphological changes were observed in hypoxic versus controls. At ED12 there was a significant increase (48%) in Bcl-2 levels at the end of the hypoxic treatment, followed by a significant increase of active caspase-9 (49%) and active caspase-3 (58%) at 30 and 60 min p-h, respectively, while at ED18 no significant changes were observed. These findings indicate that prenatal hypoxia produces an equilibrated imbalance in both pro- and anti-apoptotic proteins that culminates in a process of cell death, present at earlier stages of development.
KeywordsHypoxia Apoptosis Caspase-3 Programmed cell death Chick optic lobe CNS development
This work was supported by grants from the Consejo Nacional de Investigaciones Científicas y Técnicas and Universidad de Buenos Aires. Authors thank, Lic. Valentina Sorzzoni, Dr. Silvia Trejo and Alba Mitridate de Novara for histological technical assistance and Damián Vacotto for assistance with illustrations.
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