Loss of parathyroid hormone-stimulated 1,25-dihydroxyvitamin D3 production in aging does not involve protein kinase A or C pathways.
Loss of parathyroid hormone-stimulated 1,25-dihydroxyvitamin D3 production in aging does not involve protein kinase A or C pathways.
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衰老过程中甲状旁腺激素刺激的 1,25-二羟基维生素 D3 产生的丧失不涉及蛋白激酶 A 或 C 途径。
DOI：
10.1002/jbmr.5650090308
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发表时间：
1994
期刊：
影响因子：
--
通讯作者：
Favus,MJ
中科院分区：
文献类型：
--
作者：
Friedlander,J;Janulis,M;Tembe,V;Ro,HK;Wong,MS;Favus,MJ
由于肾脏1，25-二羟维生素D3[1，25-（OH）2D 3]生物合成减少，肠道钙吸收随年龄增长而下降。至少部分1，25-（OH）2D 3的下降可能是由于对甲状旁腺激素（PTH）刺激肾25-羟基维生素D1-羟化酶（1-OHase）活性的获得性抵抗。为了测试衰老大鼠是否可以增加PTH引起的1，25-（OH）2D 3产生，给同一窝雄性大鼠喂食正常钙饮食，并在175-225 g（年轻大鼠）或3个月后在350-425 g（衰老大鼠）时处死。处死时，老龄动物的基础血清1，25-（OH）2D 3水平（88 ± 16 vs 49 ± 8 pg/ml，P< 0.05）和体外肾近端小管1-OHase活性（178 ± 15 vs 77 ± 5 pmol/mg蛋白/5分钟，n= 6，P< 0.001）较低。rPTH-（1-34）（10 - 11或10 - 11 M）在体外增加年轻大鼠（但不增加衰老大鼠）灌流肾近端小管的1，25-（OH）2D 3分泌。对于年轻和衰老大鼠，rPTH-（1-34）（10 - 7 M）增加近曲小管cAMP依赖性蛋白激酶（PKA）活性，较低浓度（10 - 11 M）刺激蛋白激酶C（PKC）活性从胞浆转移到可溶性膜近曲小管细胞组分。本研究的结果表明，PTH激活1，25-（OH）2D 3的产生可能涉及两种信号通路，其中PKC通路对较低浓度的激素有反应。在衰老过程中对PTH刺激1，25-（OH）2D 3产生的获得性抵抗似乎不涉及PKA或PKC的激素激活。
Intestinal calcium absorption declines with aging as a result of decreased renal 1,25‐dihydroxyvitamin D3[1,25‐(OH)2D3] biosynthesis. At least part of the decline in 1,25‐(OH)2D3may be due to acquired resistance to parathyroid hormone (PTH) stimulation of renal 25‐hydroxyvitamin D1‐hydroxylase (1‐OHase) activity. To test whether aging rats can increase 1,25‐(OH)2D3production in response to PTH, male rats of the same litter were fed a normal Ca diet and were sacrificed at 175–225 g (young rats) or 3 months later at 350–425 g (aging rats). At sacrifice, basal serum 1,25‐(OH)2D3levels (88 ± 16 versus 49 ± 8 pg/ml,P< 0.05) and in vitro renal proximal tubule 1‐OHase activity (178 ± 15 versus 77 ± 5 pmol/mg protein/5 minutes,n= 6,P< 0.001) were lower in aging animals. rPTH‐(1–34) (10−11or 10−11M) increased in vitro 1,25‐(OH)2D3secretion by perifused renal proximal tubules from young but not aging rats. For young and aging rats, rPTH‐(1–34) (10−7M) increased proximal tubule cAMP‐dependent protein kinase (PKA) activity, and lower concentrations (10−11M) stimulated translocation of protein kinase C (PKC) activity from cytosolic to soluble membrane proximal tubule cell fractions. The results of this study show that PTH activation of 1,25‐(OH)2D3production may involve both signaling pathways, with the PKC pathway responsive to lower concentrations of the hormone. The acquired resistance to PTH stimulation of 1,25‐(OH)2D3production in aging appears not to involve the hormonal activation of PKA or PKC.