HEAT-SHOCK-PROTEIN-27 - DEVELOPMENTAL REGULATION AND EXPRESSION AFTERPERIPHERAL-NERVE INJURY

The heat shock protein (HSP) 27 is constitutively expressed at low lev els in medium-sized lumbar dorsal root ganglion (DRG) cells in adult r ats. Transection of the sciatic nerve results in a ninefold upregulati on of HSP27 mRNA and protein in axotomized neurons in the ipsilateral DRG at 48 hr, without equivalent changes in the mRNAs encoding HSP56, HSP60, HSP70, and HSP90. Dorsal rhizotomy, injuring the central axon o f the DRG neuron, does not upregulate HSP27 mRNA levers. After periphe ral axotomy, HSP27 mRNA and protein are present in small, medium, and large DRG neurons, and HSP27 protein is transported anterogradely, acc umulating in the dorsal horn and dorsal columns of the spinal cord, wh ere it persists for several months. Axotomized motor neurons also upre gulate HSP27. Only a minority of cultured adult DRG neurons are HSP27- immunoreactive soon after dissociation, but all express HSP27 after 24 hr in culture with prominent label throughout the neuron, including t he growth cone. HSP27 differs from most axonal injury-regulated and gr owth-associated genes, which are typically present at high levels in e arly development and downregulated on innervation of their targets, in that its mRNA is first detectable in the DRG late in development and only approaches adult levels by postnatal day 21. In non-neuronal cell s, HSP27 has been shown to be involved both in actin filament dynamics and in protection against necrotic and apoptotic cell death. Therefor e, its upregulation after adult peripheral nerve injury may both promo te survival of the injured neurons and contribute to alterations in th e cytoskeleton associated with axonal growth.