title: Alteration in expression of myosin isoforms in detrusor smooth muscle following bladder outlet obstruction.
abstract: Partial urinary bladder outlet obstruction (PBOO) in men, secondary to benign prostatic hyperplasia, induces detrusor smooth muscle (DSM) hypertrophy. However, despite DSM hypertrophy, some bladders become severely dysfunctional (decompensated). Using a rabbit model of PBOO, we found that although DSM from sham-operated bladders expressed nearly 100% of both the smooth muscle myosin heavy chain isoform SM-B and essential light chain isoform LC17a, DSM from severely dysfunctional bladders expressed as much as 75% SM-A and 40% LC17b (both associated with decreased maximum velocity of shortening). DSM from dysfunctional bladder also exhibited tonic-type contractions, characterized by slow force generation and high force maintenance. Immunofluorescence microscopy showed that decreased SM-B expression in dysfunctional bladders was not due to generation of a new cell population lacking SM-B. Metabolic cage monitoring revealed decreased void volume and increased voiding frequency correlated with overexpression of SM-A and LC17b. Myosin isoform expression and bladder function returned toward normal upon removal of the obstruction, indicating that the levels of expression of these isoforms are markers of the PBOO-induced dysfunctional bladders.
authors.affiliation: 3010 Ravdin-Courtyard, HUP, Univ. of Pennsylvania, 3400 Spruce St., Philadelphia, PA 19104, USA.
authors.forename: Michael E
authors.initials: ME
authors.lastname: DiSanto
authors.forename: Raimund
authors.initials: R
authors.lastname: Stein
authors.forename: Shaohua
authors.initials: S
authors.lastname: Chang
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Hypolite
authors.forename: Yongmu
authors.initials: Y
authors.lastname: Zheng
authors.forename: Stephen
authors.initials: S
authors.lastname: Zderic
authors.forename: Alan J
authors.initials: AJ
authors.lastname: Wein
authors.forename: Samuel
authors.initials: S
authors.lastname: Chacko
mesh_terms: D000818:Animals; D015415:Biomarkers; D015153:Blotting, Western; D004195:Disease Models, Animal; D015180:Electrophoresis, Gel, Two-Dimensional; D005455:Fluorescent Antibody Technique; D008297:Male; D009119:Muscle Contraction / Q000502:physiology; D009130:Muscle, Smooth / Q000378:metabolism* / Q000503:physiopathology; D018995:Myosin Heavy Chains / Q000096:biosynthesis; D018994:Myosin Light Chains / Q000096:biosynthesis; D009218:Myosins / Q000096:biosynthesis*; D009924:Organ Culture Techniques; D020033:Protein Isoforms / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000032:analysis; D011817:Rabbits; D020133:Reverse Transcriptase Polymerase Chain Reaction; D001748:Urinary Bladder Neck Obstruction / Q000378:metabolism* / Q000503:physiopathology
chemical_list: D015415:Biomarkers; D018994:Myosin Light Chains; D020033:Protein Isoforms; D012333:RNA, Messenger; D018995:Myosin Heavy Chains; D009218:Myosins