The purified and reconstituted ornithine/citrulline carrier from rat liver mitochondria: electrical nature and coupling of the exchange reaction with H+ translocation

Indiveri, Cesare; Tonazzi, Annamaria; Stipani, Italo; Palmieri, Ferdinando

doi:10.1042/bj3270349

Cited by 51 publications

(39 citation statements)

References 30 publications

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“…It should be noted that while arginase I is located in the cell cytosol, where ODC is also located, facilitating polyamine synthesis from ornithine, arginase II is a mitochondrial enzyme that could preferentially enhance proline or glutamate synthesis from ornithine, because ornithine aminotransferase is also located in the mitochondria (31). However, it has been shown that proline can be converted to ornithine (31) and that ornithine can be transported from the mitochondria to the cytosol (32). Consistent with our findings for H. pylori stimulation, upregulation of arginase II has been reported for RAW 264.7 cells activated by LPS (33) or cAMP (34) and in peritoneal macrophages stimulated by LPS (35).…”

Section: Discussionmentioning

confidence: 99%

Helicobacter pylori Induces Macrophage Apoptosis by Activation of Arginase II

Gobert

Cheng

Wang

et al. 2002

The Journal of Immunology

157

201

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Helicobacter pylori infection induces innate immune responses in macrophages, contributing to mucosal inflammation and damage. Macrophage apoptosis is important in the pathogenesis of mucosal infections but has not been studied with H. pylori. NO derived from inducible NO synthase (iNOS) can activate macrophage apoptosis. Arginase competes with iNOS by converting l-arginine to l-ornithine. Since we reported that H. pylori induces iNOS in macrophages, we now determined whether this bacterium induces arginase and the effect of this activation on apoptosis. NF-κB-dependent induction of arginase II, but not arginase I, was observed in RAW 264.7 macrophages cocultured with H. pylori. The time course of apoptosis matched those of both arginase and iNOS activities. Surprisingly, apoptosis was blocked by the arginase inhibitors Nω-hydroxy-l-arginine or Nω-hydroxy-nor-l-arginine, but not by the iNOS inhibitor N-iminoethyl-l-lysine. These findings were confirmed in peritoneal macrophages from iNOS-deficient mice and were not dependent on bacterial-macrophage contact. Ornithine decarboxylase (ODC), which metabolizes l-ornithine to polyamines, was also induced in H. pylori-stimulated macrophages. Apoptosis was abolished by inhibition of ODC and was restored by the polyamines spermidine and spermine. We also demonstrate that arginase II expression is up-regulated in both murine and human H. pylori gastritis tissues, indicating the likely in vivo relevance of our findings. Therefore, we describe arginase- and ODC-dependent macrophage apoptosis, which implicates polyamines in the pathophysiology of H. pylori infection.

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Section: Discussionmentioning

confidence: 99%

Helicobacter pylori Induces Macrophage Apoptosis by Activation of Arginase II

Gobert

Cheng

Wang

et al. 2002

The Journal of Immunology

157

201

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“…For example, differential expression of the arginase isoenzymes could provide a means to preferentially direct ornithine either to proline or glutamate synthesis via OAT or to polyamine synthesis via ODC (Figure 2). If so, this would imply that ornithine does not rapidly equilibrate between cytosolic and mitochondrial compartments, despite the existence of transporters via which ornithine can traverse the mitochondrial membrane [204][205][206][207][208]. So far as we are aware, no experiments to determine the effect of arginase localization on the metabolic fates of ornithine have been performed.…”

Section: Arginasementioning

confidence: 99%

Arginine metabolism: nitric oxide and beyond

Morris

1998

Biochemical Journal

2,450

2,036

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Arginine is one of the most versatile amino acids in animal cells, serving as a precursor for the synthesis not only of proteins but also of nitric oxide, urea, polyamines, proline, glutamate, creatine and agmatine. Of the enzymes that catalyse rate-controlling steps in arginine synthesis and catabolism, argininosuccinate synthase, the two arginase isoenzymes, the three nitric oxide synthase isoenzymes and arginine decarboxylase have been recognized in recent years as key factors in regulating newly identified aspects of arginine metabolism. In particular, changes in the activities of argininosuccinate synthase, the arginases, the inducible isoenzyme of nitric oxide synthase and also cationic amino acid transporters play major roles in determining the metabolic fates of arginine in health and disease, and recent studies have identified

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“…This possibility is in accord with the notion that under physiological conditions ureagenesis depends upon mitochondrial ornithine availability and the transport of ornithine into hepatic mitochondria (24 -26). This is especially true when mitochondrial ornithine uptake is inhibited by other amino acids (26) or when the mitochondrial ornithine carrier is affected by H ϩ (27,28). Ureagenesis begins in mitochondria and finishes in the cytosol (18).…”

mentioning

confidence: 99%