25-HYDROXYCHOLECALCIFEROL STIMULATION OF MUSCLE METABOLISM
25-HYDROXYCHOLECALCIFEROL STIMULATION OF MUSCLE METABOLISM
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DOI：
10.1172/jci108184
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发表时间：
1975-01-01
影响因子：
15.9
通讯作者：
HADDAD, JG
中科院分区：
文献类型：
--
作者：
BIRGE, SJ;HADDAD, JG
将维生素 D 缺乏大鼠的完整隔膜与 [3H]亮氨酸在体外培养。孵育前 7 小时口服 10 杯 (400 U) 胆钙化醇，可使亮氨酸掺入膈肌蛋白的量增加 136%（P 小于 0.001），而未经治疗的动物的制备物。肾切除术并没有消除这种反应。服用维生素后 7 小时，膈肌的 ATP 含量也有所增加。给予胆钙化醇4小时后，血清磷浓度比未治疗动物降低0.7 mg/100 ml（P小于0.025），膈肌无机32PO4积累率增加18%（P小于0.025）。通过膳食补充磷酸盐 3 天来增加维生素 D 缺乏动物的血清磷酸盐浓度，未能显着增强亮氨酸与蛋白质的结合。然而，在致软骨病、缺乏维生素 D 的饮食中补充磷 3 周，刺激了动物和肌肉 ATP 水平的增长。由于在饮食中添加磷而导致的生长和肌肉 ATP 含量的增加小于通过在饮食中添加磷和维生素 D 所实现的生长和肌肉 ATP 水平的增加。为了消除维生素的全身影响，将维生素 D 耗尽的大鼠前腿的滑车上肌维持在组织培养中。在培养基中添加 20 ng/ml 25-羟基胆钙化醇 (25-OHD3) 可增强肌肉的 ATP 含量并增加亮氨酸与蛋白质的结合。浓度为20μg/ml的维生素D3和浓度为500pg/ml的1,25-二羟基胆钙化醇(1,25-(OH)2D3)没有效果。对蔗糖密度梯度中的肌肉胞质溶胶的分析揭示了特异性结合 25-OHD3 的蛋白质部分，并且其对 1,25-(OH)2D3 的亲和力较低。这些研究表明25-OHD3可能直接影响肌肉细胞内磷酸盐的积累，从而在维持肌肉代谢和功能中发挥重要作用。
Intact diaphragms from vitamin D-deficient rats were incubated in vitro with [3H]leucine. Oral administration of 10 mug (400 U) of cholecalciferol 7 h before incubation increased leucine incorporation into diaphragm muscle protein by 136% (P less than 0.001) of the preparation from untreated animals. Nephrectomy did not obliterate this response. ATP content of the diaphragm muscle was also enhanced 7 h after administration of the vitamin. At 4 h after administration of cholecalciferol, serum phosphorus concentration was reduced by 0.7 mg/100 ml (P less than 0.025) and the rate of inorganic 32PO4 accumulation by diaphragm muscle was increased by 18% (P less than 0.025) over the untreated animals. Increasing serum phosphate concentration of the vitamin D-deficient animals by dietary supplementation with phosphate for 3 days failed to significantly enhance leucine incorporation into protein. However, supplementation of the rachitogenic, vitamin D-deficient diet with phosphorus for 3 wk stimulated the growth of the animal and muscle ATP levels. This increase in growth and muscle ATP content attributed to the addition of phosphorus to the diet was less than the increase in growth and muscle ATP levels achieved by the addition of both phosphorus and vitamin D to the diet. To eliminate systemic effects of the vitamin, the epitrochlear muscle of the rat foreleg of vitamin D-depleted rats was maintained in tissue culture. Addition of 20 ng/ml of 25-hydroxycholecalciferol (25-OHD3) to the medium enhanced ATP content of the muscle and increased leucine incorporation into protein. Vitamin D3 at a concentration of 20 mug/ml and 1,25-dihydroxycholecalciferol (1,25-(OH)2D3) at a concentration of 500 pg/ml were without effect. Analysis of muscle cytosol in sucrose density gradients revealed a protein fraction which specifically bound 25-OHD3 and which demonstrated a lesser affinity for 1,25-(OH)2D3. These studies suggest that 25-OHD3 may influence directly the intracellular accumulation of phosphate by muscle and thereby play an important role in the maintenance of muscle metabolism and function.