Alteration of the PKC-mediated signaling pathway for smooth muscle contraction in obstruction-induced hypertrophy of the urinary bladder.
Alteration of the PKC-mediated signaling pathway for smooth muscle contraction in obstruction-induced hypertrophy of the urinary bladder.
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DOI：
10.1038/labinvest.2009.38
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发表时间：
2009-07
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影响因子：
--
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中科院分区：
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正常的膀胱功能需要逼尿肌(DSM)的收缩和放松。在人和动物模型中，由于部分膀胱出口梗阻(PBOO)，DSM经历了代偿性肥大。膀胱肥大后，膀胱要么保持其正常功能(代偿)，要么功能失调(代偿失调)，排尿频率增加，尿量减少。我们分析了兔PBOO模型DSM的收缩特性。蛋白激酶C(PKC)激动剂佛波醇12，13-二丁酸酯(PDBu)可引起正常或代偿膀胱的DSM条类似程度的收缩。然而，在失代偿膀胱的DSM条上，PDBu引起的收缩显著减少。失代偿膀胱中PKCα的表达和活性也最低。PKC特异性抑制剂双吲哚马来酰亚胺(Bis)可阻断PDBu诱导的收缩和PKC活性。此外，在失代偿膀胱的DSM中，磷酸化蛋白抑制剂CPI-17的磷酸化程度降低，这将导致CPI-17对肌球蛋白轻链磷酸酶活性的抑制作用减弱，从而导致收缩能力降低。免疫组织化学染色显示PKC和磷酸化CPI-17在DSM中共存，并证实这些信号蛋白在失代偿膀胱中的减少。我们的结果表明，PKC介导的DSM收缩与PKC的表达、活性和CPI-17的磷酸化有相应的变化。我们的发现表明，膀胱功能与PKC通路之间存在显著的相关性。PKC通路受损似乎与失代偿膀胱的严重功能障碍有关。
Normal urinary bladder function requires contraction and relaxation of the detrusor smooth muscle (DSM). The DSM undergoes compensatory hypertrophy in response to partial bladder outlet obstruction (PBOO) in both men and animal models. Following bladder hypertrophy, the bladder either retains its normal function (compensated) or becomes dysfunctional (decompensated) with increased voiding frequency and decreased void volume. We analyzed the contractile characteristics of DSM in a rabbit model of PBOO. The protein kinase C (PKC) agonist Phorbol 12, 13-dibutyrate (PDBu) elicited similar levels of contraction of DSM strips from normal or compensated bladders. However, PDBu-induced contraction decreased significantly in DSM strips from decompensated bladders. The expression and activity of PKC α were also lowest in decompensated bladders. The PKC specific inhibitor bisindolylmaleimide-1 (Bis) blocked PDBu-induced contraction and PKC activity in all three groups. Moreover, the phosphorylation of the phosphoprotein inhibitor CPI-17 was diminished in DSM from the decompensated bladder, which would result in less inhibitory potency of CPI-17 on myosin light chain phosphatase activity and contribute to less contractility. Immunostaining revealed the co-localization of PKC and phosphorylated CPI-17 in the DSM and confirmed the decreases of these signaling proteins in the decompensated bladder. Our results show a differential PKC-mediated DSM contraction with corresponding alterations of PKC expression, activity and the phosphorylation of CPI-17. Our finding suggests a significant correlation between bladder function and PKC pathway. An impaired PKC pathway appears to be correlated with bladder severe dysfunction observed in decompensated bladders.
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影响因子：
5.5
作者：
DiSanto, ME;Stein, R;Chacko, S
通讯作者：
Chacko, S
DOI：
10.1152/ajpcell.2001.280.2.c254
发表时间：
2001-02-01
影响因子：
5.5
作者：
Hypolite, JA;DiSanto, ME;Chacko, S
通讯作者：
Chacko, S
影响因子：
20.1
作者：
Seko, T;Ito, M;Nakano, T
通讯作者：
Nakano, T
影响因子：
56.9
作者：
DILLON, PF;AKSOY, MO;MURPHY, RA
通讯作者：
MURPHY, RA
影响因子：
5
作者：
Arai, M;Suzuki, T;Nagai, R
通讯作者：
Nagai, R