title: Caspase-3 activation in astrocytes following postnatal excitotoxic damage correlates with cytoskeletal remodeling but not with cell death or proliferation.
abstract: Caspase-3 has classically been defined as the main executioner of programmed cell death. However, recent data supports the participation of this protease in non-apoptotic cellular events including cell proliferation, cell cycle regulation, and cellular differentiation. In this study, astroglial cleavage of caspase-3 was analyzed following excitotoxic damage in postnatal rats to determine if its presence is associated with apoptotic cell death, cell proliferation, or cytoskeletal remodeling. A well-characterized in vivo model of excitotoxicity was studied, where damage was induced by intracortical injection of N-methyl-D-asparate (NMDA) in postnatal day 9 rats. Our results demonstrate that cleaved caspase-3 was mainly observed in the nucleus of activated astrocytes in the lesioned hemisphere as early as 4 h postlesion and persisted until the glial scar was formed at 7-14 days, and it was not associated with TUNEL labeling. Caspase-3 enzymatic activity was detected at 10 h and 1 day postlesion in astrocytes, and co-localized with caspase-cleaved fragments of glial fibrillary acidic protein (CCP-GFAP). However, at longer survival times, when astroglial hypertrophy was observed, astroglial caspase-3 did not generally correlate with GFAP cleavage, but instead was associated with de novo expression of vimentin. Moreover, astroglial caspase-3 cleavage was not associated with BrdU incorporation. These results provide further evidence for a nontraditional role of caspases in cellular function that is independent of cell death and suggest that caspase activation is important for astroglial cytoskeleton remodeling following cellular injury.
authors.affiliation: Medical Histology, Department of Cell Biology, Physiology and Immunology, Faculty of Medicine and Institute of Neurosciences, Autonomous University of Barcelona, Spain. Laia.acarin@uab.es
authors.forename: Laia
authors.initials: L
authors.lastname: Acarin
authors.forename: Sonia
authors.initials: S
authors.lastname: Villapol
authors.forename: Maryam
authors.initials: M
authors.lastname: Faiz
authors.forename: Troy T
authors.initials: TT
authors.lastname: Rohn
authors.forename: Bernardo
authors.initials: B
authors.lastname: Castellano
authors.forename: Berta
authors.initials: B
authors.lastname: González
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D001921:Brain / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D001925:Brain Damage, Chronic / Q000201:enzymology* / Q000503:physiopathology; D053148:Caspase 3 / Q000378:metabolism*; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects; D048429:Cell Size / Q000187:drug effects; D003599:Cytoskeleton / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005911:Gliosis / Q000139:chemically induced* / Q000201:enzymology / Q000503:physiopathology; D007382:Intermediate Filaments / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D016202:N-Methylaspartate / Q000378:metabolism / Q000633:toxicity; D009410:Nerve Degeneration / Q000139:chemically induced / Q000201:enzymology / Q000503:physiopathology; D009498:Neurotoxins / Q000378:metabolism / Q000633:toxicity; D051381:Rats; D020318:Rats, Long-Evans; D014746:Vimentin / Q000378:metabolism
chemical_list: D005904:Glial Fibrillary Acidic Protein; D009498:Neurotoxins; D014746:Vimentin; D016202:N-Methylaspartate; D053148:Caspase 3