title: Cellular mechanisms of the age-related decrease in renal phosphate reabsorption.
abstract: 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 contransporter (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 32-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-Pi cotransport activity, which was associated with similar decreases in BBM NaPi-2 protein abundance and renal cortical NaPi-2 mRNA level. Immunohisto-chemistry 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.
authors.affiliation: Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, USA.
authors.forename: V
authors.initials: V
authors.lastname: Sorribas
authors.forename: M
authors.initials: M
authors.lastname: Lötscher
authors.forename: J
authors.initials: J
authors.lastname: Loffing
authors.forename: J
authors.initials: J
authors.lastname: Biber
authors.forename: B
authors.initials: B
authors.lastname: Kaissling
authors.forename: H
authors.initials: H
authors.lastname: Murer
authors.forename: M
authors.initials: M
authors.lastname: Levi
mesh_terms: D000222:Adaptation, Physiological / Q000502:physiology; D000375:Aging / Q000502:physiology*; D000818:Animals; D015152:Blotting, Northern; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry; D007668:Kidney / Q000378:metabolism* / Q000648:ultrastructure; D007687:Kidney Tubules, Proximal / Q000378:metabolism; D008297:Male; D010710:Phosphates / Q000378:metabolism*; D016226:Phosphorus, Dietary / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D050608:Sodium-Phosphate Cotransporter Proteins; D050610:Sodium-Phosphate Cotransporter Proteins, Type II; D027981:Symporters
chemical_list: D002352:Carrier Proteins; D010710:Phosphates; D016226:Phosphorus, Dietary; D012333:RNA, Messenger; D050608:Sodium-Phosphate Cotransporter Proteins; D050610:Sodium-Phosphate Cotransporter Proteins, Type II; D027981:Symporters