title: Role of heat shock protein 27 in cytoskeletal remodeling of the airway smooth muscle cell.
abstract: Remodeling of the airway smooth muscle (ASM) cell has been proposed to play an important role in airway hyperresponsiveness. Using a functional assay, we have assessed remodeling of the cultured rat ASM cell and the role of heat shock protein (HSP) 27 in that process. To probe remodeling dynamics, we measured spontaneous motions of an individual Arg-Gly-Asp-coated microbead that was anchored to the cytoskeleton. We reasoned that the bead could not move unless the microstructure to which it is attached rearranged; if so, then its mean square displacement (MSD) would report ongoing internal reorganizations over time. Each bead displayed a random, superdiffusive motion; MSD increased with time as approximately t(1.7), whereas an exponent of unity would be expected for a simple passive diffusion. Increasing concentrations of cytochalasin-D or latrunculin-A caused marked increases in the MSD, whereas colchicine did not. Treatments with PDGF or IL-1beta, but not transforming growth factor-beta, caused decreases in the MSD, the extent of which rank-ordered with the relative potency of these agents in eliciting the phosphorylation of HSP27. The chemical stressors anisomycin and arsenite each increased the levels of HSP27 phosphorylation and, at the same time, decreased bead motions. In particular, arsenite prevented and even reversed the effects of cytochalasin-D on bead motions. Finally, ASM cells overexpressing phospho-mimicking human HSP27, but not wild-type or phosphorylation-deficient HSP27, exhibited decreases in bead motions that were comparable to the arsenite response. Taken together, these results show that phosphorylated HSP27 favors reduced bead motions that are probably due to stabilization of the actin cytoskeleton.
authors.affiliation: Physiology Program, Department of Environmental Health, Harvard School of Public Health, Boston, MA 02115. san@hsph.harvard.edu
authors.forename: Steven S
authors.initials: SS
authors.lastname: An
authors.forename: Ben
authors.initials: B
authors.lastname: Fabry
authors.forename: Mathew
authors.initials: M
authors.lastname: Mellema
authors.forename: Predrag
authors.initials: P
authors.lastname: Bursac
authors.forename: William T
authors.initials: WT
authors.lastname: Gerthoffer
authors.forename: Usamah S
authors.initials: US
authors.lastname: Kayyali
authors.forename: Matthias
authors.initials: M
authors.lastname: Gaestel
authors.forename: Stephanie A
authors.initials: SA
authors.lastname: Shore
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Fredberg
mesh_terms: D000818:Animals; D000841:Anisomycin / Q000494:pharmacology; D018053:Arsenites / Q000494:pharmacology; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D002478:Cells, Cultured; D020099:Coated Materials, Biocompatible; D015638:Cytochalasin D / Q000494:pharmacology; D003599:Cytoskeleton / Q000187:drug effects / Q000502:physiology*; D004058:Diffusion; D005260:Female; D006133:Growth Substances / Q000494:pharmacology; D006360:Heat-Shock Proteins / Q000378:metabolism / Q000502:physiology*; D007375:Interleukin-1 / Q000494:pharmacology; D008387:Marine Toxins / Q000494:pharmacology; D008863:Microspheres; D009038:Motion; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000502:physiology*; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D009842:Oligopeptides; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013844:Thiazoles / Q000494:pharmacology; D053778:Thiazolidines; D014132:Trachea / Q000166:cytology / Q000187:drug effects / Q000502:physiology*
chemical_list: D018053:Arsenites; D019086:Bridged Bicyclo Compounds, Heterocyclic; D020099:Coated Materials, Biocompatible; D006133:Growth Substances; D006360:Heat-Shock Proteins; D007375:Interleukin-1; D008387:Marine Toxins; D019384:Nucleic Acid Synthesis Inhibitors; D009842:Oligopeptides; D013844:Thiazoles; D053778:Thiazolidines; D015638:Cytochalasin D; D000841:Anisomycin; C047981:arginyl-glycyl-aspartic acid; C015001:arsenite; C037067:latrunculin A