title: Myosin, transgelin, and myosin light chain kinase: expression and function in asthma.
abstract: BACKGROUND
  Airway smooth muscle (SM) of patients with asthma exhibits a greater velocity of shortening (Vmax) than that of normal subjects, and this is thought to contribute to airway hyperresponsiveness. A greater Vmax can result from increased myosin activation. This has been reported in sensitized human airway SM and in models of asthma. A faster Vmax can also result from the expression of specific contractile proteins that promote faster cross-bridge cycling. This possibility has never been addressed in asthma.
  
  
  OBJECTIVE
  We tested the hypothesis that the expression of genes coding for SM contractile proteins is altered in asthmatic airways and contributes to their increased Vmax.
  
  
  METHODS
  We quantified the expression of several genes that code for SM contractile proteins in mild allergic asthmatic and control human airway endobronchial biopsies. The function of these contractile proteins was tested using the in vitro motility assay.
  
  
  RESULTS
  We observed an increased expression of the fast myosin heavy chain isoform, transgelin, and myosin light chain kinase in patients with asthma. Immunohistochemistry demonstrated the expression of these genes at the protein level. To address the functional significance of this overexpression, we purified tracheal myosin from the hyperresponsive Fisher rats, which also overexpress the fast myosin heavy chain isoform as compared with the normoresponsive Lewis rats, and found a faster rate of actin filament propulsion. Conversely, transgelin did not alter the rate of actin filament propulsion.
  
  
  CONCLUSIONS
  Selective overexpression of airway smooth muscle genes in asthmatic airways leads to increased Vmax, thus contributing to the airway hyperresponsiveness observed in asthma.
authors.affiliation: Meakins-Christie Laboratories, McGill University, 3626 St-Urbain street, Montreal, PQ, H2X 2P2 Canada.
authors.forename: Renaud
authors.initials: R
authors.lastname: Léguillette
authors.forename: Michel
authors.initials: M
authors.lastname: Laviolette
authors.forename: Celine
authors.initials: C
authors.lastname: Bergeron
authors.forename: Nedjma
authors.initials: N
authors.lastname: Zitouni
authors.forename: Paul
authors.initials: P
authors.lastname: Kogut
authors.forename: Julian
authors.initials: J
authors.lastname: Solway
authors.forename: Linda
authors.initials: L
authors.lastname: Kachmar
authors.forename: Qutayba
authors.initials: Q
authors.lastname: Hamid
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Lauzon
mesh_terms: D000293:Adolescent; D000818:Animals; D001249:Asthma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D001706:Biopsy; D015153:Blotting, Western; D001999:Bronchoscopy; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D005500:Follow-Up Studies; D015870:Gene Expression; D020022:Genetic Predisposition to Disease; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008840:Microfilament Proteins / Q000096:biosynthesis / Q000235:genetics*; D009124:Muscle Proteins / Q000096:biosynthesis / Q000235:genetics*; D009130:Muscle, Smooth / Q000378:metabolism* / Q000473:pathology; D018995:Myosin Heavy Chains / Q000096:biosynthesis / Q000235:genetics*; D009219:Myosin-Light-Chain Kinase / Q000096:biosynthesis / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics*; D051381:Rats; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew; D029867:Xenopus Proteins
chemical_list: D008840:Microfilament Proteins; D009124:Muscle Proteins; D012333:RNA, Messenger; D029867:Xenopus Proteins; C051615:transgelin; D009219:Myosin-Light-Chain Kinase; D018995:Myosin Heavy Chains