O'Connell T D, Weishaar R E, Simpson R U
Department of Pharmacology, University of Michigan, Ann Arbor 48109-0626.
Endocrinology. 1994 Feb;134(2):899-905. doi: 10.1210/endo.134.2.8299585.
In this report, we demonstrate a significant inverse correlation between contractility and serum 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] levels and no correlation between contractility and serum levels of calcium, phosphate, or PTH. We also examined myosin isozyme distribution in vitamin D3-deficient rats, because myosin isozyme distribution can alter contractility. There was a significant increase in the levels of the V1 myosin isozyme in animals raised on a vitamin D3-deficient diet that maintained normal serum calcium and phosphate levels. There was no difference in the relative myosin isozyme distribution in animals raised on a hypocalcemia-yielding vitamin D3-deficient diet vs. animals raised on a control diet. As increased contractility has been observed in both groups of vitamin D3-deficient animals, a shift in myosin isozyme distribution cannot solely explain the increase in contractility previously observed in the vitamin D3-deficient rat heart. To determine whether 1,25-(OH)2D3 directly regulates myosin isozyme levels, we analyzed myosin isozyme distribution in primary cultures of ventricular myocytes. We found that 1,25-(OH)2D3 reduces total myosin levels, but does not alter myosin isozyme distribution. Thus, we show that the influence of vitamin D3 status on myosin isozyme expression in the intact rat involves a complex regulatory system of direct and indirect effects.
在本报告中，我们证明了收缩性与血清1,25 - 二羟基维生素D3 [1,25-(OH)2D3]水平之间存在显著的负相关，而收缩性与血清钙、磷或甲状旁腺激素水平之间无相关性。我们还研究了维生素D3缺乏大鼠的肌球蛋白同工酶分布，因为肌球蛋白同工酶分布可改变收缩性。在以维持正常血清钙和磷水平的维生素D3缺乏饮食饲养的动物中，V1肌球蛋白同工酶水平显著升高。在以导致低钙血症的维生素D3缺乏饮食饲养的动物与以对照饮食饲养的动物之间，相对肌球蛋白同工酶分布没有差异。由于在两组维生素D3缺乏的动物中均观察到收缩性增加，因此肌球蛋白同工酶分布的改变不能单独解释先前在维生素D3缺乏大鼠心脏中观察到的收缩性增加。为了确定1,25-(OH)2D3是否直接调节肌球蛋白同工酶水平，我们分析了心室肌细胞原代培养物中的肌球蛋白同工酶分布。我们发现1,25-(OH)2D3可降低总肌球蛋白水平，但不改变肌球蛋白同工酶分布。因此，我们表明维生素D3状态对完整大鼠肌球蛋白同工酶表达的影响涉及直接和间接效应的复杂调节系统。
