title: Over expression of smooth muscle thin filament associated proteins in the bladder wall of diabetics.
abstract: OBJECTIVE
  The thin filament associated proteins caldesmon, tropomyosin and calponin have been shown to modulate actin-myosin interaction, actomyosin adenosine triphosphatase and contraction in smooth muscle. This study was performed to determine whether the expression of these proteins is altered in diabetes induced decrease in the contractility of bladder wall smooth muscle.
  
  
  METHODS
  Detrusor samples were obtained from New Zealand White male rabbits with alloxan induced diabetes, and from age and sex matched control rabbits. In addition, a bladder myocyte cell line, which continues to express smooth muscle phenotype, was exposed to either normal (5 mM) or high (50 mM) concentrations of glucose. The levels of expression of the thin filament associated proteins were determined at the mRNA and protein levels by reverse transcriptase-polymerase chain reaction and Western blotting, respectively.
  
  
  RESULTS
  Detrusor smooth muscle tissue from rabbits with alloxan induced diabetes showed over expression of thin filament associated proteins, calponin, tropomyosin and caldesmon when compared with that of the control. Similar up-regulation was seen also in bladder myocytes in cultures treated with 50 mM glucose, indicating that the high glucose induced the changes.
  
  
  CONCLUSIONS
  Our results suggest that the increased expression of thin filament proteins, calponin, tropomyosin and caldesmon in diabetic rabbits might alter the contractile and cytoskeletal structure in bladder myocytes. The over expression of these thin filament associated proteins, which suppresses actin-myosin interaction and actomyosin adenosine triphosphatase, and the enhancement of this suppression by tropomyosin are likely to have an effect on the relationship between force and myosin light chain phosphorylation, requiring higher levels of phosphorylation in diabetic detrusor compared with that of control. The downstream effects of high glucose (eg oxidative stress) appear to modulate the transcriptional regulation of thin filament mediated regulatory proteins in bladder smooth muscle.
authors.affiliation: Division of Urology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Anita S
authors.initials: AS
authors.lastname: Mannikarottu
authors.forename: Arun K
authors.initials: AK
authors.lastname: Changolkar
authors.forename: Michael E
authors.initials: ME
authors.lastname: Disanto
authors.forename: Alan J
authors.initials: AJ
authors.lastname: Wein
authors.forename: Samuel
authors.initials: S
authors.lastname: Chacko
mesh_terms: D000818:Animals; D002135:Calcium-Binding Proteins / Q000096:biosynthesis*; D002148:Calmodulin-Binding Proteins / Q000096:biosynthesis*; D003920:Diabetes Mellitus / Q000378:metabolism*; D005786:Gene Expression Regulation; D008297:Male; D008840:Microfilament Proteins; D009124:Muscle Proteins / Q000096:biosynthesis*; D009130:Muscle, Smooth / Q000378:metabolism*; D011817:Rabbits; D014335:Tropomyosin / Q000096:biosynthesis*; D001743:Urinary Bladder / Q000378:metabolism*; D000096985:Calponins
chemical_list: D002135:Calcium-Binding Proteins; D002148:Calmodulin-Binding Proteins; D008840:Microfilament Proteins; D009124:Muscle Proteins; D014335:Tropomyosin; D000096985:Calponins