title: Survivin and heat shock protein 25/27 colocalize with cleaved caspase-3 in surviving reactive astrocytes following excitotoxicity to the immature brain.
abstract: Following immature excitotoxic brain damage, distinct patterns of caspase activation have been described in neurons and glial cells. Neuronal cells show activation of the mitochondrial apoptosis pathway, caspase-3 cleavage and apoptotic cell death, while reactive astrocytes show caspase-3 cleavage that is not always correlated with enzymatic protease activity and does not generally terminate in cell death. Accordingly, the aim of the present study was to evaluate the astrocytic colocalization of cleaved caspase-3 and several anti-apoptotic proteins of the inhibitor of apoptosis proteins family (IAPs), such as survivin and cellular inhibitor of apoptosis-2 (cIAP-2), and the heat shock proteins (HSPs) family, Hsp25/27 and Hsc70/Hsp70, which can all prevent caspases from cleaving their substrates. At several survival times ranging from 4 h to 14 days after cortical excitotoxic damage induced by N-methyl-d-aspartate (NMDA) injection at postnatal day 9 in rat pups, single and double immunohistochemical techniques were performed in free floating cryostat sections and sections were analyzed by confocal microscopy. Our results show that survivin and Hsp25/27 are primarily expressed in reactive astrocytes of the damaged cortex and the adjacent white matter. In addition, both molecules strongly colocalize with cleaved caspase-3. Survivin is primarily located in the nucleus, like cleaved caspase-3; while Hsp25/27 is cytoplasmic but very frequently found in cells showing nuclear caspase-3. cIAP-2 was mostly found in damaged neurons but also in some glial scar reactive astrocytes and showed fewer correlation with caspase-3. Hsc70/Hsp70 was only expressed in injured neurons and did not correlate with caspase-3. Thus, we conclude that primarily survivin and Hsp25/27 may participate in the inhibition of cleaved caspase-3 in reactive astrocytes and may be involved in protecting astrocytes after injury.
authors: Medical Histology, Torre M5, Department of Cell Biology, Physiology and Immunology, Institute of Neuroscience, Faculty of Medicine, Autonomous University of Barcelona, Bellaterra 08193, Barcelona, Spain. sonia.villapol@uab.es
authors: S
authors: S
authors: Villapol
authors: L
authors: L
authors: Acarin
authors: M
authors: M
authors: Faiz
authors: B
authors: B
authors: Castellano
authors: B
authors: B
authors: Gonzalez
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D001921:Brain / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D053148:Caspase 3 / Q000378:metabolism*; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D003593:Cytoplasm / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005911:Gliosis / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D055551:HSP27 Heat-Shock Proteins; D050884:HSP72 Heat-Shock Proteins / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000378:metabolism*; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism; D008297:Male; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D016202:N-Methylaspartate / Q000494:pharmacology; D009363:Neoplasm Proteins / Q000378:metabolism*; D009410:Nerve Degeneration / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009498:Neurotoxins / Q000494:pharmacology; D051381:Rats; D020318:Rats, Long-Evans; D000077022:Survivin
chemical_list: C516989:Birc5 protein, rat; D055551:HSP27 Heat-Shock Proteins; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins; C486114:Hspb1 protein, rat; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D009498:Neurotoxins; D000077022:Survivin; D016202:N-Methylaspartate; D053148:Caspase 3