Increased expression and processing of caspase-12 after traumatic brain injury in rats.
Traumatic brain injury (TBI) disrupts tissue homeostasis resulting in pathological apoptotic activation. Recently, caspase-12 was reported to be induced and activated by the unfolded protein response following excess endoplasmic reticulum (ER) stress. This study examined rat caspase-12 expression using the controlled cortical impact TBI model. Immunoblots of fractionalized cell lysates found elevated caspase-12 proform (approximately 60 kDa) and processed form (approximately 12 kDa), with peak induction observed within 24 h post-injury in the cortex (418% and 503%, respectively). Hippocampus caspase-12 proform induction peaked at 24 h post-injury (641%), while processed form induction peaked at 6 h (620%). Semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) analysis confirmed elevated caspase-12 mRNA levels after TBI. Injury severity (1.0, 1.2 or 1.6 mm compression) was associated with increased caspase-12 mRNA expression, peaking at 5 days in the cortex (657%, 651% and 1259%, respectively) and 6 h in the hippocampus (435%, 451% and 460%, respectively). Immunohistochemical analysis revealed caspase-12 induction in neurons in both the cortex and hippocampus as well as in astrocytes at the contusion site. This is the first report of increased expression of caspase-12 following TBI. Our results suggest that the caspase-12-mediated ER apoptotic pathway may play a role in rat TBI pathology independent of the receptor- or mitochondria-mediated apoptotic pathways.
Larner
Stephen F
SF
Department of Neuroscience, Evelyn F and William L McKnight Brain Institute of the University of Florida, Center for Traumatic Brain Injury Studies, Gainesville, Florida 32611, USA.
Hayes
Ronald L
RL
McKinsey
Deborah M
DM
Pike
Brian R
BR
Wang
Kevin K W
KK
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001930:Brain Injuries / Q000201:enzymology* / Q000473:pathology; D053454:Caspase 12; D020169:Caspases / Q000235:genetics* / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D018450:Disease Progression; D005786:Gene Expression Regulation; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D015151:Immunoblotting; D007150:Immunohistochemistry; D008297:Male; D016133:Polymerase Chain Reaction / Q000379:methods; D011499:Protein Processing, Post-Translational; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology
C506443:Casp12 protein, rat; D053454:Caspase 12; D020169:Caspases