O'Connell T D, Giacherio D A, Jarvis A K, Simpson R U
Department of Pharmacology, University of Michigan, Ann Arbor 48109-0626.
Endocrinology. 1995 Feb;136(2):482-8. doi: 10.1210/endo.136.2.7835280.
The signals that regulate cardiac myocyte maturation in the neonatal heart are not completely understood. In our study we examined the effects of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] on primary cultures of ventricular myocytes isolated from neonatal rat hearts. Our data show that 1,25-(OH)2D3 inhibited an increase in both the muscle-specific form of creatine kinase and V1 myosin isoenzyme levels in myocytes induced to mature by serum withdrawal. Thus, in contrast to other cell types studied to date, in the heart, 1,25-(OH)2D3 blocks cell maturation. Treating cultures with phorbol 12-myristate 13-acetate induced a decrease in the muscle-specific isoenzyme of creatine kinase similar to the effects of 1,25-(OH)2D3. Interestingly, we found that staurosporine, a protein kinase-C inhibitor, blunts the effects of 1,25-(OH)2D3 and has the opposite effect of phorbol 12-myristate 13-acetate on cultured myocytes induced to mature by serum withdrawal. Thus, our data identify a novel role for 1,25-(OH)2D3 in the regulation of myocardial development and suggest that 1,25-(OH)2D3 may be acting through a protein kinase-dependent mechanism to maintain cardiac myocytes in an immature state.
目前尚未完全了解调节新生心脏中心肌细胞成熟的信号。在我们的研究中，我们检测了1,25 - 二羟基维生素D3 [1,25-(OH)2D3] 对从新生大鼠心脏分离的心室肌细胞原代培养物的影响。我们的数据表明，1,25-(OH)2D3抑制了因血清撤除诱导成熟的心肌细胞中肌酸激酶的肌肉特异性形式和V1肌球蛋白同工酶水平的增加。因此，与迄今为止研究的其他细胞类型不同，在心脏中，1,25-(OH)2D3会阻断细胞成熟。用佛波酯12 - 肉豆蔻酸酯13 - 乙酸酯处理培养物会导致肌酸激酶的肌肉特异性同工酶减少，这与1,25-(OH)2D3的作用相似。有趣的是，我们发现蛋白激酶C抑制剂星形孢菌素会减弱1,25-(OH)2D3的作用，并且对因血清撤除诱导成熟的培养心肌细胞产生与佛波酯12 - 肉豆蔻酸酯13 - 乙酸酯相反的作用。因此，我们的数据确定了1,25-(OH)2D3在心肌发育调节中的新作用，并表明1,25-(OH)2D3可能通过蛋白激酶依赖性机制发挥作用，使心肌细胞维持在未成熟状态。
