Armbrecht H J, Boltz M A, Christakos S, Bruns M E
Geriatric Research, Education, and Clinical Center, Department of Veterans Affairs Medical Center, St. Louis, Missouri 63125, USA.
Arch Biochem Biophys. 1998 Apr 15;352(2):159-64. doi: 10.1006/abbi.1998.0594.
Studies in rats and humans have shown that there is an age-related decline in the stimulation of intestinal Ca transport by 1,25-dihydroxyvitamin D3 [1,25(OH)2D], the active metabolite of vitamin D. The calbindins are a family of vitamin D-dependent calcium-binding proteins found in the intestine (calbindin D-9k) and kidney (calbindin D-28k) and are thought to play a role in calcium transport and homeostasis. The purpose of this study was to determine if the capacity of 1,25(OH)2D to stimulate the expression of calbindin protein and mRNA changes with age. Young (2 months), adult (12 months), and old (22 months) male F344 rats were made deficient in 1,25(OH)2D by being fed a strontium-containing diet and then being given a single i.p. injection of 1,25(OH)2D. Calbindin protein levels were measured by immunological techniques using specific antisera, and mRNA levels were measured by Northern and dot blots. The maximal amount of calbindin D-9k protein induced by 1,25(OH)2D declined with age in the duodenum but not in the ileum. In time-course studies, there was a delay in calbindin D-9k induction in the duodenum but not in the ileum of adult rats compared to young rats. In contrast to protein induction, maximal calbindin D-9k mRNA levels in response to 1,25(OH)2D were greater in the adult animal and showed no time lag compared to those in the young animal. In the kidney, maximal levels of renal calbindin D-28k protein and mRNA did not change with age, but there was delayed induction in the adult. These studies demonstrate that there is an age-related decrease in the induction of calbindin protein in response to 1,25(OH)2D in the duodenum, but not in the ileum or kidney. This decline may be due to decreased translation of calbindin D-9k mRNA into protein in the duodenum with age.
对大鼠和人类的研究表明，维生素D的活性代谢产物1,25 - 二羟维生素D3 [1,25(OH)2D]对肠道钙转运的刺激作用存在与年龄相关的下降。钙结合蛋白是一类维生素D依赖性钙结合蛋白，存在于肠道（钙结合蛋白D - 9k）和肾脏（钙结合蛋白D - 28k）中，被认为在钙转运和体内平衡中发挥作用。本研究的目的是确定1,25(OH)2D刺激钙结合蛋白表达的能力是否随年龄变化。通过给年轻（2个月）、成年（12个月）和老年（22个月）雄性F344大鼠喂食含锶饮食，使其缺乏1,25(OH)2D，然后腹腔注射一次1,25(OH)2D。使用特异性抗血清通过免疫技术测量钙结合蛋白水平，通过Northern印迹和斑点印迹测量mRNA水平。1,25(OH)2D诱导的钙结合蛋白D - 9k蛋白的最大量在十二指肠中随年龄下降，但在回肠中没有。在时间进程研究中，与年轻大鼠相比，成年大鼠十二指肠中钙结合蛋白D - 9k的诱导延迟，但回肠中没有。与蛋白诱导相反，成年动物中对1,25(OH)2D反应的最大钙结合蛋白D - 9k mRNA水平高于年轻动物，且没有时间滞后。在肾脏中，肾钙结合蛋白D - 28k蛋白和mRNA的最大水平不随年龄变化，但成年动物中有延迟诱导。这些研究表明，十二指肠中对1,25(OH)2D反应的钙结合蛋白诱导存在与年龄相关的下降，但在回肠或肾脏中没有。这种下降可能是由于随着年龄增长，十二指肠中钙结合蛋白D - 9k mRNA翻译成蛋白质的过程减少。
