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Stress Proteins as Molecular Markers of Neurotoxicity

Department of Neurology, University of California-San Francisco and VA Medical Center, San Francisco, California 94121

Frank R. Sharp

Department of Neurology, University of California-San Francisco and VA Medical Center, San Francisco, California 94121, Department of Neurosurgery, University of California-San Francisco and VA Medical Center, San Francisco, California 94121

In response to many environmental and pathophysiologic stressful stimuli, cells undergo a stress response characterized by induction of a variety of proteins, including the heat shock protein family. The inducible heat shock protein 70 (hsp70) is believed to participate in an array of cellular activities, including cytoprotection. Normal brain cells have little detectable hsp70 RNA or protein. However, following a stressful condition hsp70 mRNA and protein are induced in different cell types depending on the severity and the nature of the stimulus. The induction of hsp70 protein correlates with the regional and cellular vulnerability to a particular injury as identified by standard histologic methods. The pattern of hsp70 expression differs in response to various neurotoxic stimuli, including hyperthermia, ischemia, seizures, hemorrhage, and N-methyl-D-aspartate receptor antagonist administration. Hsp70 expression is a useful marker of cellular injury and may help to identify previously unrecognized areas of vulnerability in the nervous system after a neurotoxic stimulus. Hsp70 may also play a neuroprotective role in the brain.

Key Words: Heat shock • hsp70 • ischemia • neuroprotection • stress response

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Toxicologic Pathology, Vol. 28, No. 1, 105-112 (2000)
DOI: 10.1177/019262330002800113


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