Alteration of contractile and regulatory proteins following partial bladder outlet obstruction.
This paper reviews the contractility and the expression of contractile and regulatory proteins in the detrusor smooth muscle (DSM) following partial bladder outlet obstruction (PBOO) in rabbits. PBOO was surgically induced by partial ligation of the urethra in adult male New Zealand White rabbits. The force generated by DSM strips from normal and obstructed bladders which showed bladder dysfunction, despite detrusor hypertrophy (decompensated bladder, DB) was measured. The expression of contractile and regulatory proteins was analyzed by reverse transcriptase-polymerase chain reaction and Western blotting. The DSM from obstructed DB revealed an overexpression of SM-A myosin heavy chain isoform (associated with decreased maximum velocity of shortening). DSM from sham-operated rabbits showed phasic contractions, whereas the detrusor from DB was tonic, exhibiting slow development of force, a longer duration of force maintenance, and slow relaxation. Rho-kinase inhibitor Y-27632 enhanced the relaxation of precontracted (with 125 mM KCl) DSM strips from DB. The enhancement of relaxation of DB by Y-27632 was associated with dephosphorylation of myosin light chain. The detrusor from normal bladders expresses predominantly the smooth muscle caldesmon (h-CaD), a thin filament-associated protein. However, the DSM from DB shows an overexpression of l-CaD, the non-muscle isoform of CaD. The l-CaD colocalizes with myosin in the cytoplasmic filaments in myocytes. These results show that the alteration of contractility of the detrusor following PBOO is associated with changes in the expression of proteins that form the contractile apparatus and regulate the actomyosin ATPase activity and contraction.
Chacko
Samuel
S
Department of Pathobiology, University of Pennsylvania, Philadelphia, 19104, USA. chackosk@mail.med.upenn.edu
Chang
Shaohua
S
Hypolite
Joseph
J
Disanto
Michael
M
Wein
Alan
A
D000818:Animals; D002148:Calmodulin-Binding Proteins / Q000502:physiology*; D009130:Muscle, Smooth / Q000503:physiopathology*; D011817:Rabbits; D024745:Smooth Muscle Myosins / Q000502:physiology*; D001748:Urinary Bladder Neck Obstruction / Q000503:physiopathology*
D002148:Calmodulin-Binding Proteins; D024745:Smooth Muscle Myosins