Phosphorus intake regulates intestinal function and polyamine metabolism in uremia.
This study found that 5/6-nephrectomized uremic rats showed secondary hyperparathyroidism as reflected by an increase in their serum parathyroid hormone (PTH) level in association with a decrease in serum 1,25-dihydroxyvitamin D [1,25-(OH)2D]. These changes recovered partially upon phosphorus restriction. Calcium absorption and gene expression of calbindin-D9k were decreased in uremia and were also improved by phosphorus restriction. In uremia, intestinal spermidine/spermine N1-acetyltransferase activity was decreased, while ornithine decarboxylase (ODC) activity and its gene expression were potentiated. Enhancement of c-fos and c-jun gene expressions was also observed in uremia. These phenomena suggest that the intestinal villus may proliferate in uremia. Phosphorus restriction prevented increases in the expression of ODC, c-fos and c-jun observed in uremia. Since phosphorus restriction caused a rise in the serum 1,25-(OH)2D level, the role of 1,25-(OH)2D in uremia-induced intestinal dysfunction was examined. A single injection of 1,25-(OH)2D3 to uremic rats caused an increase in the steady-state calbindin-D9k mRNA level, and decreases in steady state c-fos and ODC mRNA levels, suggesting that the deficiency of 1,25-(OH)2D3 is responsible for intestinal dysfunction in uremia. In conclusion, altered polyamine metabolism caused by 1,25-(OH)2D deficiency is intimately involved in intestinal dysfunction and the development of the proliferative state of the intestinal villus in uremia.
Imanishi
Y
Y
Department of Biochemistry, Osaka City University Medical School, Japan.
Koyama
H
H
Inaba
M
M
Okuno
S
S
Nishizawa
Y
Y
Morii
H
H
Otani
S
S
D000042:Absorption / Q000502:physiology; D000818:Animals; D001806:Blood Urea Nitrogen; D001835:Body Weight; D064026:Calbindins; D002118:Calcium / Q000097:blood; D002136:Calcium, Dietary / Q000378:metabolism; D004032:Diet; D004195:Disease Models, Animal; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D007413:Intestinal Mucosa / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism / Q000601:surgery; D007676:Kidney Failure, Chronic / Q000378:metabolism; D009392:Nephrectomy; D009419:Nerve Tissue Proteins / Q000235:genetics; D010281:Parathyroid Hormone / Q000097:blood; D010710:Phosphates / Q000097:blood; D016226:Phosphorus, Dietary / Q000493:pharmacokinetics*; D011073:Polyamines / Q000378:metabolism*; D011519:Proto-Oncogenes / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D064030:S100 Calcium Binding Protein G / Q000235:genetics; D014511:Uremia / Q000378:metabolism*; D014807:Vitamin D / Q000031:analogs & derivatives / Q000097:blood / Q000494:pharmacology
D064026:Calbindins; D002136:Calcium, Dietary; D009419:Nerve Tissue Proteins; D010281:Parathyroid Hormone; D010710:Phosphates; D016226:Phosphorus, Dietary; D011073:Polyamines; D012333:RNA, Messenger; D064030:S100 Calcium Binding Protein G; C576508:S100g protein, rat; D014807:Vitamin D; C097949:1,25-dihydroxyvitamin D; D002118:Calcium