title: Cell-specific DNA fragmentation may be attenuated by a survivin-dependent mechanism after traumatic brain injury in rats.
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.
authors.affiliation: Center for Traumatic Brain Injury Studies (CTBIS), E.F and W.L. McKnight Brain Institute of the University of Florida, Gainesville, FL 32610, USA.
authors.forename: Erik A
authors.initials: EA
authors.lastname: Johnson
authors.forename: Stanislav I
authors.initials: SI
authors.lastname: Svetlov
authors.forename: Kevin K W
authors.initials: KK
authors.lastname: Wang
authors.forename: Ronald L
authors.initials: RL
authors.lastname: Hayes
authors.forename: Jose A
authors.initials: JA
authors.lastname: Pineda
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001253:Astrocytes / Q000378:metabolism; D015153:Blotting, Western / Q000379:methods; D001930:Brain Injuries / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism*; D002452:Cell Count / Q000379:methods; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004789:Enzyme Activation / Q000502:physiology; D007839:Functional Laterality / Q000502:physiology; D005786:Gene Expression Regulation / Q000502:physiology*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D020287:In Situ Nick-End Labeling / Q000379:methods; D008297:Male; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008954:Models, Biological; D009474:Neurons / Q000378:metabolism; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: D005904:Glial Fibrillary Acidic Protein; D008869:Microtubule-Associated Proteins; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases; D010751:Phosphopyruvate Hydratase