Book of Abstracts - Australian Centre for Economic Research on ...

23-26 August 2007,
Budapest, Hungary
5B_04_S
NEUROPROTECTIVE EFFECTS OF EXTRACELLULAR HSP70
Michael Tytell
Neurobiology & Anatomy, Wake Forest Univ. School <strong>of</strong> Med., Winston-Salem, NC 27157
e-mail: tytellm@wfu.edu
When the cytoprotective function <strong>of</strong> Hsps was a relatively new concept in the 1980s, we and Hightower
respectively observed that Hsp70 was passed from one cell to another and released into the extracellular fluid
(Tytell & Lasek, Brain Res 324:223, 1984; Hightower & Guidon, J Cell Physiol 138:257, 1989). These were
unexpected results because the Hsp70 family was thought to be exclusively intracellular proteins. In the two
decades since, extracellular Hsp70 has become well-documented. Our 1984 observation that glial Hsp70 was
transferred into the axon led to the novel hypothesis that, in the nervous system at least, the stress tolerance
<strong>of</strong> neurons was not solely dependent on their own Hsp70, but could be supplemented by additional Hsp70
from adjacent glia. For neurons, this hypothesis has major implications because those with long axons (mm
to meters in length) require newly synthesized proteins to be transported from the neuronal cell body to
remain functional. If stress or injury occurs in axons at some distance from their cell bodies, hours to days are
required <strong>for</strong> newly synthesized Hsp70 to reach the injury site, which is too long to be <strong>of</strong> use. Thus, supplying
Hsp70 at the injury site would be more effective in maintaining neuronal and axonal function. We have tested
this idea in a number <strong>of</strong> models. . In the injured sciatic nerve, local application <strong>of</strong> Hsp70 improved sensory
and motor neuron survival. Similarly, in the light-damaged rat eye, Hsp70 injected into the vitreous chamber
promoted survival <strong>of</strong> photoreceptors. In cultured glia and neurons, we found that glia released Hsp70 and
that neurons took up Hsp70 from the medium, leading to greater resistance to apoptosis induced chemically
or by lack <strong>of</strong> trophic factor. There<strong>for</strong>e, Hsp70 has potential as a therapeutic agent in acute nervous system
injury.
248