Caspase 7: increased expression and activation after traumatic brain injury in rats.
Caspases, a cysteine proteinase family, are required for the initiation and execution phases of apoptosis. It has been suggested that caspase 7, an apoptosis executioner implicated in cell death proteolysis, is redundant to the main executioner caspase 3 and it is generally believed that it is not present in the brain or present in only minute amounts with highly restricted activity. Here we report evidence that caspase 7 is up-regulated and activated after traumatic brain injury (TBI) in rats. TBI disrupts homeostasis resulting in pathological apoptotic activation. After controlled cortical impact TBI of adult male rats we observed, by semiquantitative real-time PCR, increased mRNA levels within the traumatized cortex and hippocampus peaking in the former about 5 days post-injury and in the latter within 6-24 h of trauma. The activation of caspase 7 protein after TBI, demonstrated by immunoblot by the increase of the active form of caspase 7 peaking 5 days post-injury in the cortex and hippocampus, was found to be up-regulated in both neurons and astrocytes by immunohistochemistry. These findings, the first to document the up-regulation of caspase 7 in the brain after acute brain injury in rats, suggest that caspase 7 activation could contribute to neuronal cell death on a scale not previously recognized.
Larner
Stephen F
SF
Center for Traumatic Brain Injury Studies, Department of Neuroscience, MKnight Brain Institute of the University of Florida, Gainesville, 32610, USA. sflarner@ufl.eu
McKinsey
Deborah M
DM
Hayes
Ronald L
RL
W Wang
Kevin K
KK
D000818:Animals; D017209:Apoptosis / Q000235:genetics; D001930:Brain Injuries / Q000201:enzymology* / Q000235:genetics / Q000473:pathology*; D053179:Caspase 7; D020169:Caspases / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism*; D002540:Cerebral Cortex / Q000201:enzymology / Q000473:pathology; D004789:Enzyme Activation / Q000502:physiology; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D006624:Hippocampus / Q000201:enzymology / Q000473:pathology; D008297:Male; D016716:PC12 Cells; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley
D012333:RNA, Messenger; D053179:Caspase 7; D020169:Caspases