Caspase-3 Activation in Astrocytes Following Postnatal Excitotoxic Damage Correlates with Cytoskeletal Remodeling but Not with Cell Death or Proliferation
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.
Acarin, Laia; Villapol, Sonia; Faiz, Maryam; Rohn, Troy T.; Castellano, Bernardo; and González, Berta. (2007). "Caspase-3 Activation in Astrocytes Following Postnatal Excitotoxic Damage Correlates with Cytoskeletal Remodeling but Not with Cell Death or Proliferation". Glia, 55(9), 954-965. http://dx.doi.org/10.1002/glia.20518