Overexpression of inducible Hsp70 has been shown to provide protection from cerebral ischemia both in animal models of stroke and in cell culture models. New work suggests that there are multiple routes of cell death, including apoptotic and necrotic cell death. Hsp70 is known to protect from both necrotic and apoptotic cell death. In addition to the well-studied role of Hsp70 as a molecular chaperone assisting in correct protein folding, several new mechanisms by which Hsp70 can prevent cell death have been described. Hsp70 is now known to regulate apoptotic cell death both directly by interfering with the function of several proteins that induce apoptotic cell death as well as indirectly by increasing levels of the anti-death protein bcl-2. Despite these new insights into the ways in which Hsp70 functions as an anti-death protein, further surprises are likely as we continue to gain insight into the functioning of this multifaceted protein.
From the Departments of Anesthesia and Neurosurgery (Dr Giffard) and the Departments of Neurosurgery and Neurology (Dr Yenari), Stanford University School of Medicine, Stanford, California.
Received for publication March 11, 2003;
Accepted August 28, 2003.
This work supported in part by grants from the NIH RO1GM49831 and PO1NS37520 to R.G.G., a grant from the International Anesthesia Research Society to R.G.G., and NIH grant RO1NS40516 to M.A.Y.
Reprints: Rona G. Giffard, PhD, MD, Department of Anesthesia, Grant Building, S272, Stanford University School of Medicine, Stanford, CA 94305 (e-mail: email@example.com).