Hypoxia-induced Cell Death and Activation of Pro- and Anti-apoptotic Proteins in Developing Chick Optic Lobe
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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.
- 5.Korsmeyer SJ (1999) BCL-2 gene family and the regulation of programmed cell death. Cancer Res 59:S1693–S1700Google Scholar
- 12.Cao G, Minami M, Pei W, Yan C, Chen D, O’Horo C, Graham SH, Chen J (2001) Intracellular Bax translocation after transient cerebral ischemia: implications for a role of the mitochondrial apoptotic signaling pathway in ischemic neuronal death. J Cereb Blood Flow Metab 21:321–333PubMedCrossRefGoogle Scholar
- 29.Million D, Zillner P, Baumann R (1991) Oxygen pressure-dependent control of carbonic anhydrase synthesis in chick embryonic erythrocytes. Am J Physiol 261:1188–1196Google Scholar
- 33.Kelly S, Zhao H, Sun GH, Cheng D, Qiao Y, Luo J, Martin K, Steinberg GK, Harrison SD, Yenari MA (2004) Glycogen synthase kinase 3β inhibitor Chir025 reduces neuronal death resulting from oxygen-glucose deprivation, glutamate excitotoxicity, and cerebral ischemia. Exp Neurol 188:378–386PubMedCrossRefGoogle Scholar