Cell-specific DNA fragmentation may be attenuated by a survivin-dependent mechanism after traumatic brain injury in rats

Exp Brain Res. 2005 Nov;167(1):17-26. doi: 10.1007/s00221-005-2362-2. Epub 2005 Oct 29.

Abstract

Survivin attenuates apoptosis by inhibiting cleavage of some cell proteins by activated caspase-3. We recently discovered strong up-regulation of survivin, primarily in astrocytes and a sub-set of neurons, after traumatic brain injury (TBI) in rats. In this study we characterized co-expression of survivin with activated caspase-3 and downstream DNA fragmentation (TUNEL) in astrocytes and neurons after TBI. Western blot analysis revealed significant time-dependent increases in active caspase-3 between 5 and 14 days post-injury. No difference was observed between the proportion of survivin-positive and survivin-negative cells labeled with active caspase-3 at 5 or 7 days post-injury, as indicated by dual fluorescent immunostaining. Labeling of survivin-negative cells with TUNEL was, however, significantly greater than for survivin-positive cells, suggesting that expression of survivin may attenuate DNA cleavage and progression of apoptosis. A higher proportion of astrocytes than neurons accumulated active caspase-3. In contrast, co-localization with TUNEL was significantly higher for neurons than for astrocytes. These data suggest that survivin expression may attenuate DNA cleavage and cell death, and that this mechanism operates in a cell type-specific manner after TBI.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Apoptosis / physiology
  • Astrocytes / metabolism
  • Blotting, Western / methods
  • Brain Injuries / metabolism*
  • Brain Injuries / pathology
  • Brain Injuries / physiopathology
  • Caspase 3
  • Caspases / metabolism*
  • Cell Count / methods
  • Cerebral Cortex / metabolism
  • Cerebral Cortex / pathology
  • Disease Models, Animal
  • Enzyme Activation / physiology
  • Functional Laterality / physiology
  • Gene Expression Regulation / physiology*
  • Glial Fibrillary Acidic Protein / metabolism
  • Hippocampus / metabolism
  • Hippocampus / pathology
  • In Situ Nick-End Labeling / methods
  • Male
  • Microtubule-Associated Proteins / metabolism*
  • Models, Biological
  • Neurons / metabolism
  • Phosphopyruvate Hydratase / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Time Factors

Substances

  • Glial Fibrillary Acidic Protein
  • Microtubule-Associated Proteins
  • Casp3 protein, rat
  • Caspase 3
  • Caspases
  • Phosphopyruvate Hydratase