Concomitant Down-regulation of L-arginine Transport and Nitric Oxide (NO) Synthesis in Rat Alveolar Macrophages by the Polyamine Spermine

Mössner, Jutta; Hammermann, Rainer; Racké, Kurt

doi:10.1006/pupt.2001.0297

Cited by 27 publications

(21 citation statements)

References 35 publications

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“…There is a report of inhibition of CAT2 mRNA expression by spermine in LPS-stimulated alveolar macrophages, but the partial inhibition of CAT2 mRNA did not correlate with a more substantial effect of spermine on L-Arg uptake 35. There is also evidence of spermine inhibiting transport activity of a potassium channel without altering its expression 36.…”

Section: Discussionmentioning

confidence: 96%

Polyamines Impair Immunity to Helicobacter pylori by Inhibiting L-Arginine Uptake Required for Nitric Oxide Production

et al. 2010

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BACKGROUND & AIMS-Helicobacter pylori-induced immune responses fail to eradicate the bacterium. Nitric oxide (NO) can kill H. pylori. However, translation of inducible NO synthase (iNOS) and NO generation by H. pylori-stimulated macrophages is inhibited by the polyamine spermine derived from ornithine decarboxylase (ODC), and is dependent on availability of the iNOS substrate L-arginine (L-Arg). We determined if spermine inhibits iNOS-mediated immunity by reducing L-Arg uptake into macrophages.

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Section: Discussionmentioning

confidence: 96%

Polyamines Impair Immunity to Helicobacter pylori by Inhibiting L-Arginine Uptake Required for Nitric Oxide Production

et al. 2010

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“…Furthermore, polyamines modulate the functional activities of macrophages (44). For example, spermine inhibits proinflammatory cytokine synthesis (45)(46)(47)(48) and has been reported to down-regulate arginine transport and NOS2 expression in rat alveolar macrophages (49).…”

Section: Discussionmentioning

confidence: 99%

Arginine Transport via Cationic Amino Acid Transporter 2 Plays a Critical Regulatory Role in Classical or Alternative Activation of Macrophages

Yeramian

Martín

Serrat

et al. 2006

The Journal of Immunology

121

110

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Arginine is processed by macrophages in response to the cytokines to which these cells are exposed. Th1-type cytokines induce NO synthase 2, which metabolizes arginine into nitrites, while the Th2-type cytokines produce arginase, which converts arginine into polyamines and proline. Activation of bone marrow-derived macrophages by these two types of cytokines increases l-arginine transport only through the y+ system. Analysis of the expression of the genes involved in this system showed that Slc7A1, encoding cationic amino acid transporters (CAT)1, is constitutively expressed and is not modified by activating agents, while Slc7A2, encoding CAT2, is induced during both classical and alternative activation. Macrophages from Slc7A2 knockout mice showed a decrease in l-arginine transport in response to the two kinds of cytokines. However, while NO synthase 2 and arginase expression were unmodified in these cells, the catabolism of arginine was impaired by both pathways, producing smaller amounts of nitrites and also of polyamines and proline. In addition, the induction of Slc7A2 expression was independent of the arginine available and of the enzymes that metabolize it. In conclusion, the increased arginine transport mediated by activators is strongly regulated by CAT2 expression, which could limit the function of macrophages.

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“…Spermine was reported to interfere with NF-κB activating pathway [9] that leads to the suppression of proinflammatory cytokines synthesis including TNF, interleukins-1 and 6, and macrophage inflammatory proteins-1α and -1β (MIP-1α and MIP-1β) [8]. Taurine has been previously demonstrated in indomethacin- [17] and alendronateinduced gastric injuries [36] to suppress neutrophil infiltration.…”

Section: Discussionmentioning

confidence: 99%

“…This effect might be attributed to concomitant downregulation of NO synthesis, through suppressing neutrophil iNOS expression, and cellular L-arginine transport, through suppressing the expression of CAT-2B, a particular cationic amino acid transporter [9]. Nuclear factor-κB is an essential transcription factor for the aforementioned two processes [44], and it appears possible that spermine may interfere with this activating pathway [9].…”

Section: Discussionmentioning

confidence: 99%

“…Spermine could serve in alleviating ulcerative tissues by counterregulating proinflammatory cytokine synthesis [8], controlling of NO generation in macrophages [9], and it may serve as an antioxidant barrier to the rising levels of oxidative products in the gastric mucosa [10]. However, the effect of spermine on NO and mucin production, to our knowledge, has not yet been investigated in gastric ulcer.…”

Section: Introductionmentioning

confidence: 99%

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Modulation of indomethacin‐induced gastric injury by spermine and taurine in rats

Motawi

Elgawad

Shahin

2007

J Biochem & Molecular Tox

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This study investigated the involvement of neutrophil infiltration, nitric oxide (NO) generation, and oxidative stress in indomethacin-induced ulcer and the possible gastroprotective potentials of spermine and taurine, known for their tissue regenerating and antioxidant effects, respectively. Male Wistar albino rats (180-220 g) were allocated into a normal control group, ulcer control group (received a single dose of indomethacin 40 mg-kg p.o.), and two ulcer groups pretreated with spermine (150 mg-kg p.o. 1 h before ulcer induction) and taurine (250 mg-kg i.p. for three consecutive days before ulcer induction). The animals were killed 6 h after indomethacin administration, and the gastric juice, serum, and mucosal tissue were used for gastric injury evaluation. Both modulators significantly ameliorated the indomethacin-induced gastric lesions in glandular mucosa. Notably, spermine exhibited the most pronounced effect as manifested by great reduction in the gastric ulcer index, normalization of the elevated gastric acidity, and triggering of mucin production. Spermine and taurine were able to decrease the elevated levels of gastric myeloperoxidase, conjugated diene, and serum NO. However, the lowered tissue NO content was markedly elevated only by taurine. The antioxidant action of taurine was illustrated by restoration of the depressed content of glutathione, normalization of the inhibited activities of glutathione reductase, and superoxide dismutase. These results suggest that spermine and taurine confer significant gastroprotection against indomethacin-induced gastric injury with the priority of spermine.

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Concomitant Down-regulation of L-arginine Transport and Nitric Oxide (NO) Synthesis in Rat Alveolar Macrophages by the Polyamine Spermine

Cited by 27 publications

References 35 publications

Polyamines Impair Immunity to Helicobacter pylori by Inhibiting L-Arginine Uptake Required for Nitric Oxide Production

Polyamines Impair Immunity to Helicobacter pylori by Inhibiting L-Arginine Uptake Required for Nitric Oxide Production

Arginine Transport via Cationic Amino Acid Transporter 2 Plays a Critical Regulatory Role in Classical or Alternative Activation of Macrophages

Modulation of indomethacin‐induced gastric injury by spermine and taurine in rats

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