Alteration in expression of myosin isoforms in detrusor smooth muscle following bladder outlet obstruction.
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.
DiSanto
Michael E
ME
3010 Ravdin-Courtyard, HUP, Univ. of Pennsylvania, 3400 Spruce St., Philadelphia, PA 19104, USA.
Stein
Raimund
R
Chang
Shaohua
S
Hypolite
Joseph A
JA
Zheng
Yongmu
Y
Zderic
Stephen
S
Wein
Alan J
AJ
Chacko
Samuel
S
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
D015415:Biomarkers; D018994:Myosin Light Chains; D020033:Protein Isoforms; D012333:RNA, Messenger; D018995:Myosin Heavy Chains; D009218:Myosins