title: Protection against protein aggregation by alpha-crystallin as a mechanism of preconditioning.
abstract: Anesthetic preconditioning occurs when cells previously exposed to inhaled anesthetics are protected against subsequent injury. We hypothesize that inhaled anesthetics may cause slight protein misfolding that involves site-specific dehydration, stimulating cytoprotective mechanisms. Human neuroblastoma cells were exposed to ethanol (as the dehydration agent) followed by quantitative analysis of the expression of five heat shock genes: DNAJC5G, CRYAA, HSPB2, HSF4 and HSF2. There was an ethanol-induced upregulation of all genes except HSF4, similar to previous observations using isoflurane. CRYAA (the gene for alphaA-crystallin) exhibited a 23.19 and 17.15-fold increase at 24 and 48 h post ethanol exposure, respectively. Additionally, we exposed glyceraldehyde 3-phosphate dehydrogenase to ethanol, which altered oligomeric subspecies and caused protein aggregation in a concentration-dependent manner. Ethanol-mediated dehydration-induced protein aggregation was prevented by incubation with alpha-crystallin. These data indicate that ethanol mimics the effects of isoflurane presumably through a cellular preconditioning mechanism that involves dehydration-induced protein aggregation.
authors: Department of Anesthesiology, University of Missouri-Kansas City School of Medicine, 4401 Wornall Road, Kansas City, MO 64111, USA.
authors: Jonathan E
authors: JE
authors: Ferns
authors: Christopher S
authors: CS
authors: Theisen
authors: Eugene E
authors: EE
authors: Fibuch
authors: Norbert W
authors: NW
authors: Seidler
mesh_terms: D018685:Anesthetics, Inhalation / Q000009:adverse effects*; D001483:Base Sequence; D045744:Cell Line, Tumor; D017931:DNA Primers; D004591:Electrophoresis, Polyacrylamide Gel; D006360:Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D060888:Real-Time Polymerase Chain Reaction; D038201:alpha-Crystallins / Q000502:physiology*
chemical_list: D018685:Anesthetics, Inhalation; D017931:DNA Primers; D006360:Heat-Shock Proteins; D038201:alpha-Crystallins