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Heat shock factor 1 and heat shock proteins: critical partners in protection against acute cell injury. Crit Care Med 2002 Jan;30(1 Suppl):S43-50

Date

01/10/2002

Pubmed ID

11782560

DOI

10.1097/00003246-200201001-00006

Scopus ID

2-s2.0-0036160052   181 Citations

Abstract

OBJECTIVE: Life-threatening conditions cause severe changes in the organization and conformation of macromolecules, creating urgent requirements for protein repair to ensure survival. As molecular chaperones, heat shock proteins (HSP) that have specialized functions in protein folding are now well established to restore homeostasis in cells and organisms. Augmentation of HSP synthesis is tightly regulated by stress-inducible heat shock factors (HSF), which are part of a transcriptional signaling cascade with both positive (e.g., HSP) and negative (e.g., proinflammatory cytokines) properties. In this review, we discuss the biological roles and mechanisms of HSP-mediated protection in pathophysiologic conditions (ischemia, sepsis, and preeclampsia) and the regulation for stress-dependent HSP synthesis and speculate about future applications for harnessing HSF and HSP partners as cytoprotective agents.

DATA SOURCES: Reactive oxygen species are major pathogenic factors in cell death pathways (e.g., necrosis, apoptosis), in part, because of proteotoxic effects. In intact organisms, forced overexpression of HSP per se affords effective counterbalance against ischemia challenges (e.g., heart and brain) and systemic conditions (e.g., sepsis). Besides stressful conditions, gene-targeting studies have uncovered new functions for heat shock transcription factors (e.g., maintenance of intrauterine pregnancy) in mammals. In parallel, pharmacologic studies using small molecules are paving the way for future prospects to exploit the beneficial properties of HSP, albeit an important but presently elusive goal.

CONCLUSIONS: Together, HSF and HSP partners are attractive targets in therapeutic strategies designed to stimulate endogenous protective mechanisms against deleterious consequences of oxidative stress. With further technological advances, it is anticipated that the spotlight on HSP, alone or in combination with other stress response pathways, could, ultimately, reduce injury and accelerate functional recovery of susceptible organs in living organisms including humans.

Author List

Christians ES, Yan LJ, Benjamin IJ

Author

Ivor J. Benjamin MD Center Director, Professor in the Medicine department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Cytoprotection
DNA-Binding Proteins
Heat Shock Transcription Factors
Heat-Shock Proteins
Ischemia
Molecular Chaperones
Oxidative Stress
Sepsis
Transcription Factors
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