Blood content modulates the induction of heat shock proteins in the neurovascular network.
Heat shock proteins are ubiquitous members of a family of molecular chaperones that protect various cell populations from injury. Up-regulation of heat shock proteins, particularly the 70 kDa species, bind selectively to denatured or partially damaged polypeptides that would otherwise perturb cell function and initiate cell death programs. In this regard, induction of heat shock proteins provides protection from cerebral ischemia in animal models of stroke. Endothelial cells, in particular, are intimately involved in the above protective event as these cells mount a stress response with induction of the 70 kDa heat shock protein. However, the coupling of heat shock proteins and the neurovascular response are not yet known. Here we show that blood content is an important factor in this stress response as rats devoid of blood content do not display a heat shock response in the microvasculature of the hippocampal formation. This lack of stress response, however, is reversed when rats are reperfused with exogenous rat or human blood content. We propose a new ischemic-sensing role for blood that serves to integrate information about protein-damaging conditions and heat shock protein levels in the neurovascular network. Further characterization of this sensing role could represent an attractive new approach to treatment of global ischemia and other microvascular pathologies.
Kafel
John
J
Department of Neuroscience, New York College of Osteopathic Medicine of New York Institute of Technology, Old Westbury, NY 11568, USA.
Baldinger
Lauren
L
Chabla
Janet M
JM
Hallas
Brian H
BH
Horowitz
Judith M
JM
Torres
German
G
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D000818:Animals; D001769:Blood / Q000378:metabolism*; D001921:Brain / Q000166:cytology*; D042783:Endothelial Cells / Q000502:physiology*; D004912:Erythrocytes / Q000502:physiology; D005786:Gene Expression Regulation / Q000502:physiology*; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D008875:Middle Aged; D010949:Plasma / Q000502:physiology; D011180:Postmortem Changes; D051381:Rats; D017207:Rats, Sprague-Dawley; D015424:Reperfusion / Q000379:methods
D018840:HSP70 Heat-Shock Proteins