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Regional and Temporal Alterations in DNA Fragmentation Factor (DFF)‐Like Proteins Following Experimental Brain Trauma in the Rat
Author(s) -
Zhang Chen,
Raghupathi Ramesh,
Saatman Kathryn E.,
LaPlaca Michelle C.,
McIntosh Tracy K.
Publication year - 1999
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1999.0731650.x
Subject(s) - dna fragmentation , medicine , endocrinology , fragmentation (computing) , cortex (anatomy) , apoptosis , hippocampus , biology , chemistry , microbiology and biotechnology , programmed cell death , biochemistry , neuroscience , ecology
: DNA fragmentation, an early event in neuronal death following traumatic brain injury, may be triggered by the 40‐kDa subunit of DNA fragmentation factor (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 cleavage of DFF45 into 30‐and 11‐kDa fragments. In this study, the intracellular distribution of DFF45 and DFF40 was examined following lateral fluid percussion brain injury of moderate severity (2.4‐2.7 atm) in male Sprague‐Dawley rats. In the cytosolic fraction (S1) of the injured cortex at 2 and 24 h postinjury, 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 significantly decreased in the S1 and increased in the P1 fraction at both 2 and 24 h ( p < 0.01), which indicated a translocation of DFF40 from cytosol to nucleus. These data are the first to demonstrate that changes in DFF proteins occur after brain trauma and suggest that these changes may play a role in apoptotic cell death via caspase‐3‐DFF45/DFF40‐DNA cleavage observed following traumatic brain injury.