Löfgren Mia, Fagher Katarina, Woodard Geoffrey, Arner Anders
Department of Physiological Sciences, Lund University, Tornavägen 10, BMC F11, SE-223 62 Lund, Sweden.
J Physiol. 2002 Sep 15;543(Pt 3):757-66. doi: 10.1113/jphysiol.2002.025494.
Information on the effects of thyroid hormone on smooth muscle contractile protein expression and mechanical properties is sparse. We have addressed the following questions. (1) Can thyroxine hormone alter myosin isoform composition in smooth muscle? (2) Can a change in myosin isoform composition lead to altered mechanical properties in smooth muscle? (3) Are alterations, if occurring, equal in fast and slow smooth muscle types? Guinea-pigs were treated with thyroxine (T(4)) for 12 days. Control animals were given physiological saline solution. Maximal unloaded shortening velocity (V(max)) was measured in chemically skinned, maximally activated muscle preparations from the aorta and the taenia coli. V(max) increased following thyroxine treatment, by approximately 20 % in the taenia coli. In the aorta, no significant increase in V(max) could be detected. The sensitivity of isometric force to inorganic phosphate (P(i)) was increased in the taenia coli following thyroxine treatment. The expression of mRNA (determined with RT-PCR) for the myosin heavy chain with the seven amino acid insert increased by approximately 70 % in the aorta and about 25 % in the taenia coli following thyroxine treatment. Western blot analysis showed an increase in the inserted myosin heavy chain form in the taenia coli. Expression of mRNA for the myosin essential light chains and the corresponding proteins did not change significantly in either muscle type. No alterations in non-muscle myosin heavy chain isoforms could be detected after thyroxine treatment. In conclusion, thyroxine treatment alters the isoform composition of myosin in fast and slow smooth muscles in vivo. This change is sufficient to increase shortening velocity and sensitivity of isometric force to P(i) in the fast, but not in the slow, smooth muscle type.
关于甲状腺激素对平滑肌收缩蛋白表达及力学特性影响的信息较为匮乏。我们探讨了以下问题。(1)甲状腺激素能否改变平滑肌中的肌球蛋白异构体组成?(2)肌球蛋白异构体组成的变化能否导致平滑肌力学特性改变?(3)若发生改变,在快、慢两种平滑肌类型中是否相同?给豚鼠注射甲状腺素(T4)12天。对照动物注射生理盐水。在来自主动脉和结肠带的化学去表皮、最大激活的肌肉标本中测量最大无负荷缩短速度(Vmax)。甲状腺素处理后Vmax增加,结肠带中增加约20%。在主动脉中,未检测到Vmax有显著增加。甲状腺素处理后,结肠带中静息张力对无机磷酸盐(Pi)的敏感性增加。甲状腺素处理后,主动脉中含七个氨基酸插入片段的肌球蛋白重链mRNA表达(通过RT-PCR测定)增加约70%,结肠带中增加约25%。蛋白质印迹分析显示结肠带中插入型肌球蛋白重链形式增加。两种肌肉类型中肌球蛋白必需轻链的mRNA表达及相应蛋白质均无显著变化。甲状腺素处理后未检测到非肌肉型肌球蛋白重链异构体有改变。总之,甲状腺素处理在体内改变了快、慢平滑肌中肌球蛋白的异构体组成。这种变化足以增加快平滑肌类型的缩短速度和静息张力对Pi的敏感性,但对慢平滑肌类型则不然。