Alterations of cerebral cortex and hippocampal proteasome subunit expression and function in a traumatic brain injury rat model

Following cellular stress or tissue injury, the proteasome plays a critical role in protein degradation and signal transduction. The present study examined the β-subunit expression of constitutive proteasomes (β1, β2, and β5), immunoproteasomes (β1i, β2i, and β5i) and the 11S proteasome activator, PA28α, in the rat CNS after traumatic brain injury (TBI). Concomitant measures assessed changes in proteasome activities. Quantitative real time PCR results indicated that β1 and β2 mRNA levels were not changed, while β5 mRNA levels were significantly decreased in injured CNS following TBI. However, β1i, β2i, β5i, and PA28α mRNA levels were significantly increased in the injured CNS. Western blotting studies found that β1, β2, β5, β2i, and β5i subunit protein levels remained unchanged in the injured CNS, but β1i and PA28α protein levels were significantly elevated in ipsilateral cerebral cortex and hippocampus. Proteasome activity assays found that peptidyl glutamyl peptide hydrolase-like and chymotrypsin-like activity were significantly reduced in the CNS after TBI, and that trypsin-like proteasome activity was increased in the injured cerebral cortex. Our results demonstrated that both proteasome composition and function in the CNS were affected by trauma. Treatments that preserve proteasome function following CNS injury may be beneficial as an approach to cerebral neuroprotection.