Cellular mechanisms of the age-related decrease in renal phosphate reabsorption

被引:35
作者
Sorribas, V
Lotscher, M
Loffing, J
Biber, J
Kaissling, B
Murer, H
Levi, M
机构
[1] VET AFFAIRS MED CTR, DALLAS, TX 75216 USA
[2] UNIV TEXAS, SW MED CTR, DEPT INTERNAL MED, DALLAS, TX USA
[3] UNIV ZURICH, INST PHYSIOL, ZURICH, SWITZERLAND
[4] UNIV ZURICH, INST ANAT, ZURICH, SWITZERLAND
[5] UNIV ZARAGOZA, FAC VET, DEPT TOXICOL, ZARAGOZA, SPAIN
关键词
D O I
10.1038/ki.1996.385
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
The aging process in humans and in the rat is associated with an impairment in renal tubular reabsorption of Pi and renal tubular adaptation to a low Pi diet. The purposes of the present study were to determine whether changes in the abundance of type II Na-Pi cotransporter (NaPi-2) protein and/or mRNA play a role in the age-related decrease in Na-Pi cotransport activity, and to further determine the cellular mechanisms of impaired adaptation to a low Pi diet. In studies performed in 3- to 4-month-old young adult rats and 12- to 16-month-old aged rats we found that there was an age-related twofold decrease in proximal tubular apical brush border membrane (BBM Na-P) cotransport activity, which was associated with similar decreases in BBM NaPi-2-protein abundance and renal cortical NaPi-2 mRNA level. Immunohistochemistry showed lower NaPi-2 protein expression in the BBM of proximal tubules of superficial, midcortical, and juxtamedullary nephrons. We also found that in response to chronic (7 days) and/or acute (4 hr) feeding of a low Pi diet there were similar adaptive increases in BBM Na-Pi cotransport activity and BBM NaPi-2 protein abundance in both young and aged rats. However, BBM Na-Pi cotransport activity and BBM NaPi-2 protein abundance were still significantly lower in aged rats, in spite of a significantly lower serum Pi concentration in aged rats. The results indicate that impaired expression of the type ii renal Na-Pi cotransporter protein at the level of the apical BBM plays an important role in the age-related impairment in renal tubular reabsorption of Pi and renal tubular adaptation to a low Pi diet.
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收藏
页码:855 / 863
页数:9
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