title: Regulation of apoptotic and inflammatory cell signaling in cerebral ischemia: the complex roles of heat shock protein 70.
abstract: Although heat shock proteins have been studied for decades, new intracellular and extracellular functions in a variety of diseases continue to be discovered. Heat shock proteins function within networks of interacting proteins; they can alter cellular physiology rapidly in response to stress without requiring new protein synthesis. This review focuses on the heat shock protein 70 family and considers especially the functions of the inducible member, heat shock protein 72, in the setting of cerebral ischemia. In general, inhibiting apoptotic signaling at multiple points and up-regulating survival signaling, heat shock protein 70 has a net prosurvival effect. Heat shock protein 70 has both antiinflammatory and proinflammatory effects depending on the cell type, context, and intracellular or extracellular location. Intracellular effects are often antiinflammatory with inhibition of nuclear factor-kappaB signaling. Extracellular effects can lead to inflammatory cytokine production or induction of regulatory immune cells and reduced inflammation.
authors.affiliation: Department of Anesthesia, 300 Pasteur Drive, Grant Building S272, Stanford University School of Medicine, Stanford, California 94305-5117, USA. rona.giffard@stanford.edu
authors.forename: Rona G
authors.initials: RG
authors.lastname: Giffard
authors.forename: Ru-Quan
authors.initials: RQ
authors.lastname: Han
authors.forename: John F
authors.initials: JF
authors.lastname: Emery
authors.forename: Melissa
authors.initials: M
authors.lastname: Duan
authors.forename: Jean Francois
authors.initials: JF
authors.lastname: Pittet
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002545:Brain Ischemia / Q000378:metabolism*; D016923:Cell Death / Q000502:physiology; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D007249:Inflammation / Q000209:etiology* / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology
chemical_list: D018840:HSP70 Heat-Shock Proteins