Renal Fanconi syndrome: developmental basis for a new animal model with relevance to human disease

Roth, Karl S.; Medow, Marvin S.; Moses, Linda C.; Spencer, Patricia D.; Schwarz, Steven M.

doi:10.1016/0005-2736(89)90452-5

Cited by 10 publications

(4 citation statements)

References 22 publications

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“…The effects of maleate seem somehow related to the developmental stage of the kidney functions, since the drug does not induce any significant alteration in sugar or amino acid uptake by newborn rat renal tubules [2]. Membrane fluidity also appears to be altered in succinylacetone-treated rats [28], without significant changes in the normal morphology of glomeruli or proximal tubule regions [26]. Altered membrane permeability, essentially related to an increase in the cholesterol content and cholesterol/phospholipid molar ratio, has also been suggested as a major cause of impaired transport system functions in Basenji dogs with spontaneous idiopathic FS [5, 61.…”

Section: Discussionmentioning

confidence: 99%

Na+,K+-ATPase Expression in Maleic-Acid-Induced Fanconi Syndrome in Rats

et al. 1997

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Na+,K(+)-ATPase activity and its alpha 1 subunit protein and mRNA in kidney cortex were monitored in rats developing Fanconi syndrome after the administration of maleate. Na+,K(+)-ATPase activity was significantly lower than in saline-injected controls, although this was partially mediated by a general, non-specific decrease in the cortex protein content. 2. The low activity of the sodium pump correlated with low abundance of alpha 1 subunit mRNA and protein levels. Hsp60 protein levels were also decreased in kidney cortex from maleate-treated rats. 3. Kidney cortex brush-border membrane vesicles from maleate-treated rats showed a marked decrease in Na(+)-dependent alanine and glucose transport, which was not dependent on the Na(+)-transmembrane gradient itself, a finding which is consistent with a more stable effect at the plasma membrane level. 4. The effect of maleate may be partially non-specific and involve a great variety of proteins, but seems to be restricted to selected tissues because alpha 1 subunit Na+,K(+)-ATPase and hsp60 protein amounts were not significantly modified in livers from rats developing Fanconi syndrome. 5. These results show that maleate administration induces a low activity of selected concentrative transport systems and a decrease in Na+,K(+)-ATPase activity and expression. The combination of both effects may explain the increased excretion of most organic solutes present in rats developing Fanconi syndrome.

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Section: Discussionmentioning

confidence: 99%

Na+,K+-ATPase Expression in Maleic-Acid-Induced Fanconi Syndrome in Rats

et al. 1997

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“…SA has been shown to inhibit in vitro the overall DNAligase activity present in normal cell extracts (4) and to react nonenzymatically with proteins and free amino acids (5). SA is also able to generate glucosuria, proteinuria, and amino aciduria in adult rats (6). Moreover, it has recently been suggested that the renal dysfunction is, at least partly, related with SA (7).…”

Section: Introductionmentioning

confidence: 99%

Succinylacetone Oxidation by Oxygen/Peroxynitrite: A Possible Source of Reactive Intermediates in Hereditary Tyrosinemia Type I

Royer

Knudsen

Oliveira

et al. 2004

Chem. Res. Toxicol.

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Hereditary tyrosinemia type I (HT1) is an inborn metabolic error characterized by hepatorenal dysfunction. Affected patients excrete large quantities of succinylacetone (SA), a tyrosine catabolite believed to be involved in the pathogenesis of HT1. A growing body of evidence relates the oxidative stress observed in metabolic disorders to free radicals generated from accumulated metabolites. In this context, oxidation of SA by peroxynitrite or cytochrome c yielding reactive intermediates and products was investigated here. Both peroxynitrite and cytochrome c were able to initiate oxygen consumption by SA, which was followed by polarimetric and chemiluminescence measurements. The light emission arises from triplet carbonyls formed by the thermolysis of dioxetane intermediates, as indicated by energy transfer experiments. EPR spin-trapping studies with 2-methyl-2-nitrosopropane revealed the intermediacy of two different carbon-centered radicals, one of them originating from cleavage of the triplet carbonyl product. The pH profiles obtained by oxygen consumption, chemiluminescence, and stopped-flow spectrophotometry point to the peroxynitrite anion as the initiator of SA aerobic oxidation. Overstoichiometric formation of organic acids based on added peroxynitrite confirms the occurrence of an oxygen-dependent chain reaction, here proposed to be initiated by one electron abstraction from the enolic form of SA. The results obtained may help shed light on the role of both SA and oxidative stress in the pathogenesis of HT1.

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“…Hepatopathy · Tubulopathy · Anemia · Succinylacetoacetone · Newborn screening · NTBC Kasuistik Fall Charakteristisch für die Tyrosinämie Typ I ist die Assoziation der oben beschriebenen Lebersynthesestörung mit einer renalen Tubulopathie [19]. Diese lässt sich bereits in der Routinelaboruntersuchung mit Hypophosphatämie und Erhöhung der alkalischen Phosphatase erkennen.…”

Section: Introductionunclassified

“…Ein weiteres Leitsymptom ist die renale Tubulopathie mit renalem Phos-phatverlust und Vitamin-D-resistenter Rachitis [19]. Ein weiteres Leitsymptom ist die renale Tubulopathie mit renalem Phos-phatverlust und Vitamin-D-resistenter Rachitis [19].…”

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