Background. Dimethylarginines are inhibitors of NO synthesis and are involved in the pathogenesis of vascular diseases. In this study, we ask the question if asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) levels change during fatal and reversible acute rejection, and contribute to the pathogenesis of chronic vasculopathy

Akizuki

Albrecht

Andriambeloson

Anna Zakrzewicz

Baylis

Bedford

Boger

Boisvert

Bulau

Cardounel

Carello

Chen

Closs

Cooke

Dariusz Zakrzewicz

Desai

Esposito

Fabre

Fleck

Fliser

Grau

Hirschburger

Holler

Jacobi

Jeremy

Joles

Joosten

Kakimoto

Kielstein

Leiper

Li Volti

Lindholm

MacAllister

Miranda

Mowen

Oliver Eickelberg

Paik

Potena

Ravani

Rolf-Hasso Boedeker

Schepers

Sigrid Wilker

Tanaka

Tang

Tojo

Tullius

Vallance

Veronika Grau

Wang

Weis

Wilcken

Winfried Padberg

Yilmaz

Zakrzewicz

English

PubMed

Crossref

Nephrology Dialysis Transplantation

Dimethylarginine metabolism during acute and chronic rejection of rat renal allografts

BACKGROUND: Dimethylarginines are inhibitors of NO synthesis and are involved in the pathogenesis of vascular diseases. In this study, we ask the question if asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) levels change during fatal and reversible acute rejection, and contribute to the pathogenesis of chronic vasculopathy. METHODS: The Dark Agouti to Lewis rat strain combination was used to investigate fatal acute rejection. Fischer 344 kidneys were transplanted to Lewis rats to study reversible acute rejection episode and the process of chronic rejection. Isograft recipients and untreated Lewis rats were used as controls. l-arginine derivatives were determined by HPLC, and ADMA-metabolizing enzymes were studied by quantitative RT-PCR and western blotting. RESULTS: Renal transplantation transiently increased dimethylarginine levels independent of acute rejection. ADMA plasma levels did not importantly differ between recipients undergoing fatal or reversible acute rejection, whereas SDMA was even lower in recipients of Fisher 344 grafts. In comparison to isograft recipients, ADMA and SDMA levels were slightly elevated during reversible, but not during the process of chronic rejection. Increased dimethylarginine levels, however, did not block NO synthesis. Interestingly, protein methylation, but not ADMA degradation, was increased in allografts. CONCLUSIONS: Our data do not support the concept that renal allografts are protected from fatal rejection by dimethylarginines. Dimethylarginines may play a role in triggering chronic rejection, but a contribution to vascular remodelling itself is improbable. In contrast, differential arginine methylation of yet unknown proteins by PRMT1 may be involved in the pathogenesis of acute and chronic rejection

Zakrzewicz, D.

Zakrzewicz, A.

Wilker, S.

Boedeker, R.H.

Padberg, W.

Eickelberg, O.

Grau, V.

PuSH

Dimethylarginine metabolism during acute and chronic rejection of rat renal allografts.

A et al. Role of symmetric dimethylarginine in vascular damage by increasing ROS via store-operated calcium influx in monocytes. Nephrol Dial Transplant

A proteomic analysis of arginine-methylated protein complexes. Mol Cell Proteomics

A rapid, simple spectrophotometric method for simultaneous detection of nitrate and nitrite. Nitric Oxide

ADMA induces monocyte adhesion via activation of chemokine receptors in cultured THP-1 cells. Cytokine

ADMA: a novel risk factor that explains excess cardiovascular event rate in patients with end-stage renal disease. Atheroscler Suppl

ADMA: an emerging cardiovascular risk factor. Vasc Med

ADMA: its role in vascular disease. Vasc Med

An endogenous inhibitor of nitric oxide synthase regulates endothelial adhesiveness for monocytes.

Analysis of methylarginine metabolism in the cardiovascular system identifies the lung as a major source of ADMA.

Arginine methylation of NIP45 modulates cytokine gene expression in effector T lymphocytes. Mol Cell

Asymmetric dimethylarginine (ADMA) in vascular, renal and hepatic disease and the regulatory role of L-arginine on its metabolism. Mol Genet Metab

Asymmetric dimethylarginine (ADMA): the silent transition from an ‘uraemic toxin’ to a global cardiovascular risk molecule.

Asymmetric dimethylarginine andcardiacallograftvasculopathyprogression:modulationbysirolimus. Transplantation

Asymmetric dimethylarginine plasma concentrations differ in patients with end-stage renal disease: relationship to treatment method and atherosclerotic disease.

Asymmetrical dimethylarginine in renal disease: limits of variation or variation limits? A systematic review.

Asymmetrical dimethylarginine plasma clearance persists after acute total nephrectomy in rats.

Asymmetrical dimethylarginine predictsprogressiontodialysisanddeathinpatientswithchronickidney disease:acompeting risksmodelingapproach.JAmSocNephrol2005; 16:

Calver A et al. Accumulation of an endogenous inhibitor of nitric oxide synthesis in chronic renal failure. Lancet

Cardiac allograft vasculopathy and dysregulation of the NO synthase pathway. Arterioscler Thromb Vasc Biol

Cardiovascular biology of the asymmetric dimethylarginine:dimethylarginine dimethylaminohydrolase pathway. Arterioscler Thromb Vasc Biol

Chronic renal allograft rejection: pathophysiologic considerations. Kidney Int

Chubb A et al. Identification of two human dimethylarginine dimethylaminohydrolases with distinct tissue distributions and homology with microbial arginine deiminases.

Colocalization of demethylating enzymes and NOS and functional effects of methylarginines in rat kidney. Kidney Int

Contribution of early acute rejection episodes to chronic rejection in a rat kidney retransplantation model. Kidney Int

Decrease in the synthesis and release of calcitonin gene-related peptide in dorsal root ganglia of spontaneously hypertensive rat: role of nitric oxide synthase inhibitors.

Dimethylarginine dimethylaminohydrolaseoverexpressionsuppressesgraftcoronaryarterydisease. Circulation

Dynamics of monocytes/macrophages and T lymphocytes in acutely rejecting rat renal allografts. Cell Tissue Res

Endothelial functions improve with decrease in asymmetric dimethylarginine (ADMA) levels after renal transplantation. Transplantation

From arginine methylation to ADMA: a novel mechanism with therapeutic potential in chronic lung diseases. BMC Pulm Med

Habermeier A et al. Interference of L-arginine analogues with L-arginine transport mediated by the y+ carrier hCAT-2B. Nitric Oxide

Human recombinant erythropoietin augments serum asymmetric dimethylarginine concentrations but does not compromise nitric oxide generation in mice. Nephrol Dial Transplant

Increased asymmetric dimethylarginine serum levels are associated with acute rejection in kidney transplant recipients. Transplant Proc

Inducible nitric oxide synthase in renal transplantation. Kidney Int

Inhibition of inducible nitric oxide synthase improves graft function and reduces tubulointerstitial injury in renal allograft rejection.

Isolation and identification of N-G, N-GandN-G,N'-G-dimethyl-arginine,N-epsilon-mono-,di-,andtrimethyllysine, and glucosylgalactosyl- and galactosyl-delta-hydroxylysine from human urine. JB i o lC h e m1970;

Kaufmann A et al. Neuropeptide Y is expressed by rat mononuclear blood leukocytes and strongly downregulated during inflammation.

LiVoltiG,SorrentiV ,AcquavivaRetal.Effectof ischemia-reperfusion on renal expression and activity of N(G)-N(G)-dimethylarginine dimethylaminohydrolases. Anesthesiology

Marked increase of asymmetric dimethylarginine in patients with incipient primary chronic renal disease.

Nicotine attenuates macrophage infiltration in rat lung allografts.

Nitric oxide and the proliferation of vascular smooth muscle cells. Cardiovasc Res

Nitric oxide deficiency in chronic kidney disease.

PRMT1 is the predominant type I protein arginine methyltransferase in mammalian cells.

Protein arginine methylation in mammals: who, what, and why. Mol Cell

Protein methylase I. Purification and properties of the enzyme.

Quantitative assessment of arginine methylation in free versus protein-incorporated amino acids in vitro and in vivo using protein hydrolysis and high-performance liquid chromatography. Biotechniques

Regulation of nitric oxide synthesis by dimethylarginine dimethylaminohydrolase.

Relations between plasma asymmetricdimethylarginine(ADMA)andriskfactorsforcoronarydisease. Atherosclerosis

Renal transplantation in the rat: details of a technique.

Role of nitric oxide and superoxide in acute cardiac allograft rejection in rats.

Samouilov A et al. Evidence for the pathophysiological role of endogenous methylarginines in regulation of endothelial NO production and vascular function. JB i o lC h e m

Serum concentrations of asymmetric (ADMA) and symmetric (SDMA) dimethylarginine in renal failure patients. Kidney Int Suppl 2001; 78: S14–S18 134 D. Zakrzewicz et al.24. Fleck

Symmetric dimethylarginine (SDMA) as endogenous marker of renal function— a meta-analysis. Nephrol Dial Transplant

The impact of acute rejection episodes on long-term graft function and outcome in 1347 primary renal transplants treated by 3 cyclosporine regimens. Transplantation

Tiebosch ATet al. Nitric oxide production and nitric oxide synthase expression in acute human renal allograft rejection. Transplantation

Transplantation-induced functional/morphological changes in rat aorta allografts differ from those in arteries of rat kidney allografts.

http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3006445

Dimethylarginine metabolism during acute and chronic rejection of rat renal allografts

Abstract

Similar works

Full text

Available Versions

Crossref

PuSH