Alteration in expression of myosin isoforms in detrusor smooth muscle following bladder outlet obstruction
Alteration in expression of myosin isoforms in detrusor smooth muscle following bladder outlet obstruction
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DOI：
10.1152/ajpcell.00513.2002
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发表时间：
2003-12-01
影响因子：
5.5
通讯作者：
Chacko, S
中科院分区：
文献类型：
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作者：
DiSanto, ME;Stein, R;Chacko, S
继发于良性前列腺增生的男性部分膀胱出口梗阻（PBOO）可诱导逼尿肌平滑肌（DSM）肥大。然而，尽管DSM肥大，一些膀胱变得严重功能障碍（失代偿）。使用兔PBOO模型，我们发现，尽管来自假手术膀胱的DSM表达了近100%的平滑肌肌球蛋白重链亚型SM-B和必需轻链亚型LC 17 a，但来自严重功能障碍膀胱的DSM表达了多达75%的SM-A和40%的LC 17 b（两者均与缩短的最大速度降低相关）。来自功能障碍性膀胱的DSM也表现出强直型收缩，其特征在于缓慢的力产生和高的力维持。免疫荧光显微镜显示，减少SM-B的表达功能障碍的膀胱是不是由于产生一个新的细胞群体缺乏SM-B。代谢笼监测显示排尿量减少和排尿频率增加与SM-A和LC 17 b过表达相关。肌球蛋白亚型表达和膀胱功能恢复正常后，去除梗阻，表明这些亚型的表达水平是PBOO诱导的功能障碍性膀胱的标志物。
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.