Davis P J, Davis F B, Blas S D, Schoenl M, Edwards L
J Clin Endocrinol Metab. 1987 May;64(5):921-5. doi: 10.1210/jcem-64-5-921.
The effect of increasing donor age on the susceptibility of human red blood cell Ca2+-ATPase activity to stimulation in vitro by thyroid hormone was studied in 26 normal subjects, aged 15-81 yr. Basal enzyme activity (no added thyroid hormone) was unaffected by donor age. Group analysis, young (less than or equal to 50 yr) vs. elderly (greater than 60 yr old), revealed a 23% decrease in responsiveness of the enzyme to L-T4 (P less than 0.001). Regression analysis confirmed an age-dependent decline in thyroid hormone stimulability of Ca2+-ATPase [r = -0.42 (T4 effect) and -0.38 (T3 effect); P less than 0.01]. Red cell membrane Na,K-ATPase activity was not affected by donor age. Plasma T4 and T3 concentrations in these normal subjects also did not change with age. Possible contributions of the following mechanisms to this age-correlated change in enzyme activity were examined: altered responsiveness to calmodulin of membrane Ca2+-ATPase; membrane content of endogenous calmodulin, endogenous plasma T4 and T3 concentrations, and plasma glucose concentrations. Calmodulin responsiveness is required for iodothyronine action on the enzyme, but the calmodulin responsiveness of cells from elderly donors was not significantly different from that of cells from younger donors (P greater than 0.10). There was no relationship between membrane immunoassayable calmodulin and donor age or membrane calmodulin and Ca2+-ATPase activity. There were positive correlations between donor plasma T4 level and basal enzyme activity (P less than 0.05) and between donor plasma T3 concentration and hormone-responsive Ca2+-ATPase (P less than 0.01), but these did not contribute to the age effect. Plasma glucose previously was found to modulate red cell Ca2+-ATPase activity, but did not correlate with decreased hormone responsiveness of the enzyme in elderly donors. In conclusion, we found that the susceptibility of human red cell Ca2+-ATPase to in vitro thyroid hormone stimulation declined significantly with advancing donor age. Several possible calmodulin-dependent mechanisms for this age-dependent change were excluded, and thus, we postulate that the altered hormone sensitivity of the enzyme is membrane phospholipid mediated.
在26名年龄在15 - 81岁的正常受试者中，研究了供体年龄增加对人红细胞Ca2 + -ATP酶活性体外受甲状腺激素刺激敏感性的影响。基础酶活性（未添加甲状腺激素）不受供体年龄影响。分组分析，年轻组（小于或等于50岁）与老年组（大于60岁）比较，发现该酶对L - T4的反应性降低了23%（P < 0.001）。回归分析证实Ca2 + -ATP酶的甲状腺激素刺激能力存在年龄依赖性下降[r = -0.42（T4效应）和 -0.38（T3效应）；P < 0.01]。红细胞膜Na，K - ATP酶活性不受供体年龄影响。这些正常受试者的血浆T4和T3浓度也不随年龄变化。研究了以下机制对这种与年龄相关的酶活性变化的可能作用：膜Ca2 + -ATP酶对钙调蛋白反应性的改变；内源性钙调蛋白的膜含量、内源性血浆T4和T3浓度以及血浆葡萄糖浓度。碘甲状腺原氨酸对该酶的作用需要钙调蛋白反应性，但老年供体细胞的钙调蛋白反应性与年轻供体细胞的钙调蛋白反应性无显著差异（P > 0.10）。膜免疫可检测的钙调蛋白与供体年龄或膜钙调蛋白与Ca2 + -ATP酶活性之间无相关性。供体血浆T4水平与基础酶活性之间呈正相关（P < 0.05），供体血浆T3浓度与激素反应性Ca2 + -ATP酶之间呈正相关（P < 0.01），但这些均未对年龄效应产生影响。先前发现血浆葡萄糖可调节红细胞Ca2 + -ATP酶活性，但与老年供体中该酶激素反应性降低无关。总之，我们发现随着供体年龄的增长，人红细胞Ca2 + -ATP酶对体外甲状腺激素刺激的敏感性显著下降。排除了几种可能的钙调蛋白依赖性机制对这种年龄依赖性变化的影响，因此，我们推测该酶激素敏感性的改变是由膜磷脂介导的。
