Heat Shock Protein 27: Developmental Regulation and Expression after Peripheral Nerve Injury

Abstract

The heat shock protein (HSP) 27 is constitutively expressed at low levels in medium-sized lumbar dorsal root ganglion (DRG) cells in adult rats. Transection of the sciatic nerve results in a ninefold upregulation 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 of the DRG neuron, does not upregulate HSP27 mRNA levels. After peripheral axotomy, HSP27 mRNA and protein are present in small, medium, and large DRG neurons, and HSP27 protein is transported anterogradely, accumulating in the dorsal horn and dorsal columns of the spinal cord, where it persists for several months. Axotomized motor neurons also upregulate 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 the growth cone. HSP27 differs from most axonal injury-regulated and growth-associated genes, which are typically present at high levels in early 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 cells, HSP27 has been shown to be involved both in actin filament dynamics and in protection against necrotic and apoptotic cell death. Therefore, its upregulation after adult peripheral nerve injury may both promote survival of the injured neurons and contribute to alterations in the cytoskeleton associated with axonal growth.

Evaluation and management of peripheral nerve injury

“…HSP27 has been shown to be involved both in actin filament dynamics and in protection against necrotic and apoptotic cell death. Therefore, its upregulation after adult peripheral nerve injury may both promote survival of the injured neurons and contribute to alterations in the cytoskeleton associated with axonal growth (Costigan et al, 1998;Lewis et al, 1999). The neuron's capability to sustain regenerative attempts persists for at least 12 months after injury.…”

Administration of brain-derived neurotrophic factor suppresses the expression of heat shock protein 27 in rat retinal ganglion cells following axotomy

“…In the adult rat, Hsp27 is constitutively expressed in dorsal root ganglion (DRG) cells (Plumier et al, 1997c;Costigan et al, 1998). Following peripheral nerve axotomy in the adult rat, Hsp27 expression is further elevated in these cells and most neurons survive for months following the injury (Hopkins et al, 1998;Costigan et al, 1998;Lewis et al, 1999).…”

“…In the visual system, optic nerve transection causes only some RGCs to become Hsp27-positive whereas widespread expression of Hsp27 is detected in astrocytes in the retinorecipent layers of the superior colliculus (Krueger-Naug et al, 2002a). In the peripheral nervous system, sciatic nerve injury and vagotomy have resulted in the induction and prolonged expression of Hsp27 in the affected neurons (Costigan et al, 1998;Hopkins et al, 1998;Lewis et al, 1999). Hyperthermia causes the induction of Hsp27 primarily in astroglia throughout the CNS; in addition, hyperthermia results in Hsp27 expression in specific nuclei associated with fluid homeostasis and thermoregulation (Krueger-Naug et al, 2000).…”

The Effect of Neonatal Nerve Injury on the Expression of Heat Shock Proteins in Developing Rat Motoneurones

“…In contrast, in the adult nervous system no motoneurone death takes place following peripheral nerve injury (Lowrie et al, 1982) and most sensory neurones also survive (Coggeshall et al, 1997). Interestingly, in the adult both motor and sensory neurones have been shown to upregulate hsp27 expression following peripheral nerve injury (Costigan et al, 1998;Hopkins et al, 1998).…”