L-arginine metabolism in immune-mediated glomerulonephritis in the rat.
Low-protein diets slow the progression of some renal diseases. We recently found that dietary restriction of L-arginine markedly ameliorates disease in antithymocyte serum-induced glomerulonephritis in the rat, suggesting that L-arginine may play a key role in the beneficial effects of low-protein diets. L-arginine is metabolized by nitric oxide synthases to nitric oxide and L-citrulline or by arginase to urea and L-ornithine. L-ornithine is a precursor for polyamines, which are required for cell proliferation and for proline, an essential component of collagen. In a time course of disease, we found that inducible nitric oxide synthase gene expression and nitric oxide production were increased very early. Arginase activity was significantly increased until 5 days of disease. Ornithine decarboxylase, the rate-limiting step for polyamine synthesis, was increased at 3 days coincident with the onset of cell proliferation. Gene expression of ornithine aminotransferase, a proline synthetic enzyme, was increased from day 1, paralleling increased collagen synthesis. Thus, the three pathways of L-arginine metabolism are upregulated in a manner consistent with their possible roles in the cell lysis, cell proliferation, and collagen deposition, which characterize this model of glomerulonephritis.
Ketteler
M
M
Division of Nephrology and Hypertension, University of Utah Health Sciences Center, Salt Lake City 84132, USA.
Ikegaya
N
N
Brees
D K
DK
Border
W A
WA
Noble
N A
NA
D000818:Animals; D000961:Antilymphocyte Serum / Q000276:immunology; D001119:Arginase / Q000378:metabolism; D001120:Arginine / Q000378:metabolism*; D002455:Cell Division; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D015870:Gene Expression; D005921:Glomerulonephritis / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D007150:Immunohistochemistry; D007678:Kidney Glomerulus / Q000201:enzymology / Q000473:pathology; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D009955:Ornithine Decarboxylase / Q000378:metabolism; D009953:Ornithine-Oxo-Acid Transaminase / Q000235:genetics / Q000378:metabolism; D011392:Proline / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D000961:Antilymphocyte Serum; D012333:RNA, Messenger; D009569:Nitric Oxide; D003094:Collagen; D001120:Arginine; D011392:Proline; D009953:Ornithine-Oxo-Acid Transaminase; D001119:Arginase; D009955:Ornithine Decarboxylase