Role of thin-filament regulatory proteins in relaxation of colonic smooth muscle contraction.
Role of thin-filament regulatory proteins in relaxation of colonic smooth muscle contraction.
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DOI：
10.1152/ajpgi.00201.2009
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发表时间：
2009-11
期刊：
影响因子：
--
通讯作者：
S. Somara;R. Gilmont;K. Bitar
中科院分区：
文献类型：
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作者：
S. Somara;R. Gilmont;K. Bitar
结肠运动需要平滑肌收缩和舒张的协调调节。收缩与肌球蛋白轻链 (MLC(20)) 的磷酸化以及肌动蛋白与肌球蛋白的相互作用有关。肌动球蛋白相互作用的细丝调节由两种肌动蛋白结合调节蛋白调节：原肌球蛋白 (TM) 和钙结合蛋白 (CaD)。已知 TM 和 CaD 在促进收缩的肌动球蛋白相互作用中发挥着至关重要的作用。收缩与小热休克蛋白 HSP27 的磷酸化相关，同时伴随着 TM 和 CaD 的磷酸化。 HSP27 的磷酸化被认为是细丝收缩调节的主要调节剂。将结肠平滑肌细胞 (CSMC) 与松弛神经递质血管活性肠肽 (VIP) 预孵育可抑制 HSP27 (ser78) 的磷酸化。 HSP27 磷酸化的减弱可导致细丝介导的收缩调节的调节，从而导致松弛；因此，研究了细丝调节蛋白在松弛环境中的作用。 CSMC 与 VIP 预孵育显示 TM 和 CaD 磷酸化降低。此外，与 VIP 预孵育的 CSMC 显示 TM 与 HSP27 和磷酸化 HSP27 (ser78) 的关联减少，而 TM 与 CaD 和磷酸化 CaD 的解离减少。因此，我们提出，除了 MLC(20) 磷酸化的改变之外，松弛还与导致收缩终止的细丝介导的调节的改变有关。
Coordinated regulation of smooth muscle contraction and relaxation is required for colonic motility. Contraction is associated with phosphorylation of myosin light chain (MLC(20)) and interaction of actin with myosin. Thin-filament regulation of actomyosin interaction is modulated by two actin-binding regulatory proteins: tropomyosin (TM) and caldesmon (CaD). TM and CaD are known to play crucial role in actomyosin interaction promoting contraction. Contraction is associated with phosphorylation of the small heat shock protein HSP27, concomitant with the phosphorylation of TM and CaD. Phosphorylation of HSP27 is attributed as being the prime modulator of thin-filament regulation of contraction. Preincubation of colonic smooth muscle cells (CSMC) with the relaxant neurotransmitter vasoactive intestinal peptide (VIP) showed inhibition in phosphorylation of HSP27 (ser78). Attenuation of HSP27 phosphorylation can result in modulation of thin-filament-mediated regulation of contraction leading to relaxation; thus the role of thin-filament regulatory proteins in a relaxation milieu was investigated. Preincubation of CSMC with VIP exhibited a decrease in phosphorylation of TM and CaD. Furthermore, CSMC preincubated with VIP showed a reduced association of TM with HSP27 and with phospho-HSP27 (ser78) whereas there was reduced dissociation of TM from CaD and from phospho-CaD. We thus propose that, in addition to alteration in phosphorylation of MLC(20), relaxation is associated with alterations in thin-filament-mediated regulation that results in termination of contraction.