C. Zhang et al., Regional and temporal alterations in DNA fragmentation factor (DFF)-like proteins following experimental brain trauma in the rat, J NEUROCHEM, 73(4), 1999, pp. 1650-1659
DNA fragmentation, an early event in neuronal death following traumatic bra
in injury, may be triggered by the 40-kDa subunit of DNA fragmentation fact
or (DFF40). DFF40 is typically bound to the 45-kDa subunit of DFF (DFF45),
and activation of DFF40 may occur as a result of caspase-3-mediated cleavag
e of DFF45 into 30- and 11-kDa fragments. In this study, the intracellular
distribution of DFF45 and DFF40 was examined following lateral fluid percus
sion brain injury of moderate severity (2.4-2.7 arm) in male Sprague-Dawley
rats. In the cytosolic fraction (S1) of the injured cortex at 2 and 24 h p
ostinjury, significant decreases in the intensities of DFF45-like proteins
at 45- and 32-kDa bands and a concomitant increase in the 11-kDa bands were
observed (p < 0.05 vs, uninjured controls). A significant decrease in the
intensities of the 32-kDa band in the nuclear (P1) fraction of the injured
cortex was observed at 30 min and 2 h postinjury (p < 0.01). Concomitantly,
a decrease in DFF40 was observed in the cortical S1 fraction at 2 and 24 h
(p < 0.05) and in the P1 fraction at 30 min and 2 h postinjury (p < 0.01).
In the hippocampus, DFF45 decreased at 30 min in the P1 and 2 h in the S1
fraction (p < 0.05) and recovered by 24 h postinjury, whereas DFF40 was sig
nificantly decreased in the S1 and increased in the P1 fraction at both 2 a
nd 24 h (p < 0.01), which indicated a translocation of DFF40 from cytosol t
o nucleus. These data are the first to demonstrate that changes in DFF prot
eins occur after brain trauma and suggest that these changes may play a rol
e in apoptotic cell death via caspase-3-DFF45/DFF40-DNA cleavage observed f
ollowing traumatic brain injury.