Premium
Hypoxia induces caspase‐9 and caspase‐3 activation without neuronal death in gerbil brains
Author(s) -
Garnier Philippe,
PrigentTessier Anne,
Van Hoecke Michaël,
Bertrand Nathalie,
Demougeot Céline,
Sordet Olivier,
Swanson Raymond A.,
Marie Christine,
Beley Alain
Publication year - 2004
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.2004.03551.x
Subject(s) - gerbil , apoptosis , tunel assay , poly adp ribose polymerase , programmed cell death , caspase , caspase 3 , biology , dna fragmentation , hypoxia (environmental) , ischemia , hippocampal formation , microbiology and biotechnology , chemistry , endocrinology , medicine , biochemistry , polymerase , dna , oxygen , organic chemistry
To investigate the in vivo apoptotic machinery in oxygen deprived brain, we examined the expression of caspase‐9 and caspase‐3 in the hippocampus of Mongolian gerbils subjected to either transient hypoxia (4% O 2 for 6 min) or forebrain ischemia (10 min bilateral carotid artery occlusion) followed by 8 h to 7 days of reoxygenation or blood recirculation. Apoptotic death was characterized by isolating hippocampal genomic DNA and analysing DNA fragmentation as well as histological studies including TUNEL assay and toluidine blue staining of brain sections. The results showed that both hypoxic and ischemic gerbil brains exhibited an increase in caspase‐9 and caspase‐3 gene expression. However, no cell damage was detectable following hypoxia, while marked DNA fragmentation and extensive cell death was observed following ischemia. Moreover, although hypoxia did not lead to cell death, both hypoxia and ischemia were associated with cleavage of procaspase‐9 and procaspase‐3 and increases in their activities as well as cleavage of poly(ADP‐ribose) polymerase‐1 (PARP‐1), a major caspase‐3 substrate. These results indicate that, in vivo , even late apoptotic events such as caspase activation and PARP‐1 cleavage in hypoxic brains do not necessarily induce an irreversible commitment to apoptotic neuronal death.