Arruda Ana Paula, Oliveira Gaya M, Carvalho Denise P, De Meis Leopoldo
Instituto de Bioquímica Médica, Rio de Janiero, Brazil.
Mol Membr Biol. 2005 Nov-Dec;22(6):529-37. doi: 10.1080/09687860500412257.
The sarcoplasmic reticulum (SR) is composed of two fractions, the heavy fraction that contains proteins involved in Ca2+ release, and the light fraction enriched in Ca(2+)-ATPase (SERCA), an enzyme responsible for Ca2+ transport from the cytosol to the lumen of SR. It is known that in red muscle thyroid hormones regulate the expression of SERCA 1 and SERCA 2 isoforms. Here we show the effects of thyroid hormone on SERCA expression and distribution in light and heavy SR fractions from rabbit white and red muscles. In hyperthyroid red muscle there is an increase of SERCA 1 and a decrease of SERCA 2 expression. This is far more pronounced in the heavy than in the light SR fraction. As a result, the rates of Ca(2+)- ATPase activity and Ca(2+)-uptake by the heavy vesicles are increased. In hypothyroidism we observed a decrease in SERCA 1 and no changes in the amount of SERCA 2 expressed. This promoted a decrease of both Ca(2+)-uptake and Ca(2+)-ATPase activity. While the major differences in hyperthyroidism were found in the heavy SR fraction, the effects of hypothyroidism were restricted to light SR fraction. In white muscle we did not observe any significant changes in either hypo- or hyperthyroidism in both SR fractions. Thus, the regulation of SERCA isoforms by thyroid hormones is not only muscle specific but also varies depending on the subcellular compartment analyzed. These changes might correspond to the molecular basis of the altered contraction and relaxation rates detected in thyroid dysfunction.
肌浆网（SR）由两部分组成，重部分含有参与Ca2+释放的蛋白质，轻部分富含Ca(2+)-ATP酶（SERCA），该酶负责将Ca2+从细胞质转运到肌浆网腔。已知在红色肌肉中，甲状腺激素调节SERCA 1和SERCA 2同工型的表达。在此，我们展示了甲状腺激素对来自兔白色和红色肌肉的轻、重肌浆网部分中SERCA表达和分布的影响。在甲状腺功能亢进的红色肌肉中，SERCA 1增加而SERCA 2表达减少。这在重肌浆网部分比轻肌浆网部分更明显。结果，重囊泡的Ca(2+)-ATP酶活性和Ca(2+)-摄取率增加。在甲状腺功能减退时，我们观察到SERCA 1减少，而SERCA 2表达量无变化。这导致Ca(2+)-摄取和Ca(2+)-ATP酶活性均降低。虽然甲状腺功能亢进的主要差异见于重肌浆网部分，但甲状腺功能减退的影响仅限于轻肌浆网部分。在白色肌肉中，无论是甲状腺功能减退还是亢进，我们在两个肌浆网部分均未观察到任何显著变化。因此，甲状腺激素对SERCA同工型的调节不仅具有肌肉特异性，而且还因所分析的亚细胞区室而异。这些变化可能对应于甲状腺功能障碍中检测到的收缩和舒张速率改变的分子基础。
