Heat shock proteins, endothelin, and peripheral neuronal injury

Heat shock proteins (HSP) are important in neuroprotection after a variety of stresses or injuries. Both heat shock proteins and endothelin are upregulated after peripheral nerve injury, but HSP regulation after injury has not been systematically studied in peripheral nerve. The purpose of this study was to examine the regulation of small and large heat shock proteins after injury to rat sciatic nerve. Secondly, using a parallel tissue culture model for the sciatic nerve (PC12 cells), we examined potential regulation of heat shock proteins by endothelin. Western analysis of constricted, mobilized or unperturbed nerve was used to examine HSP abundance after injury. Semiquantitative PCR was used to examine heat shock message levels after nerve injury in the dorsal root ganglia. Cultured undifferentiated and differentiated PC12 cells were treated with endothelin, then western analysis of cytosol- and membrane-enriched fractions of these cells was used to examine heat shock protein regulation after endothelin treatment. Heat shock proteins are expressed at very low levels in unperturbed sciatic nerve. Constriction injury of the nerve results in increased expression of small and large heat shock proteins, but no upregulation of HSP message in corresponding dorsal root ganglia. Endothelin treatment of PC12 does not cause upregulation of heat shock proteins. Together these data show that a broad range of HSP is involved in endogenous response to peripheral nerve injury and deserve further study as potential neuroprotectants. Regulation of heat shock proteins after nerve injury is not likely due to endothelin signaling.