Methionine transsulfuration is increased  during sepsis in rats

Malmezat, T.; Breuillé, Denis; Pouyet, Corinne; Buffière, Caroline; Denis, Philippe; Mirand, Philippe Patureau; Obled, Christiane

doi:10.1152/ajpendo.2000.279.6.e1391

Cited by 68 publications

(45 citation statements)

References 37 publications

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“…This illustrates that caution must be exercised when only plasma kinetics are available, as in the current study. Nonetheless, deficiency of sulphur-AA has been suggested to compromise anti-inflammatory responses (41) , supported by earlier observations in sheep treated with endotoxin that showed a marked decrease in plasma methionine (42) , whereas in septic rats there was an 80 % increase in the transsulphuration pathway that leads to cysteine synthesis (43) . Although the mild endotoxaemia induced in the current sheep did not lead to altered cysteine ILR, the response to supplemental methionine was reduced during the LPS challenge.…”

Section: Discussionmentioning

confidence: 77%

Responses in whole-body amino acid kinetics to an acute, sub-clinical endotoxin challenge in lambs

et al. 2015

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Some effects of parasitism, endotoxaemia or sepsis can be mitigated by provision of extra protein. Supplemented protein may encompass a metabolic requirement for specific amino acids (AA). The current study investigates a method to identify and quantify the amounts of AA required during inflammation induced by an endotoxin challenge. One of each pair of six twin sheep was infused in the jugular vein for 20 h with either saline (control) or lipopolysaccharide (LPS, 2 ng/kg body weight per min) from Escherichia coli. Between 12 and 20 h a mixture of stable isotope-labelled AA was infused to measure irreversible loss rates. From 16 to 20 h all sheep were supplemented with a mixture of unlabelled AA infused intravenously. Blood samples were taken before the start of infusions, and then continuously over intervals between 14 and 20 h. At 20 h the sheep were euthanised, and liver and kidney samples were taken for measurement of serine-threonine dehydratase (SDH) activity. LPS infusion decreased plasma concentrations of most AA (P < 0·05; P < 0·10 for leucine and tryptophan), except for phenylalanine (which increased P = 0·022) and tyrosine. On the basis of the incremental response to the supplemental AA, arginine, aspartate, cysteine, glutamate, lysine (tendency only), glycine, methionine, proline, serine and threonine were important in the metabolic response to the endotoxaemia. The AA infusion between 16 and 20 h restored the plasma concentrations in the LPS-treated sheep for the majority of AA, except for glutamine, isoleucine, methionine, serine and valine. LPS treatment increased (P < 0·02) SDH activity in both liver and kidney. The approach allows quantification of key AA required during challenge situations.Key words: Endotoxin lipopolysaccharide: Amino acids: Irreversible loss rate: Serine-threonine dehydratase: SheepThe protein and amino acid (AA) demands of animals for normal physiological states (e.g. growth, pregnancy and lactation) are now well characterised, especially for pigs and poultry (1) and with progress made in ruminants (2) . These requirements are altered, however, in response to injury, infection and parasitic challenge. In many cases, impact of these challenges can be ameliorated and the rate of recovery improved by provision of additional protein in the diet (3)(4)(5)(6) . Often, however, the amount of protein required is not known, with consequences for both animal performance and farm economics.More importantly, protein per se may not be required, but instead the metabolic responses to the challenge may increase the demand for specific AA. For example, practical and theoretical arguments have been presented for additional arginine in cardiovascular and pulmonary disorders (7)(8)(9)(10) , for cysteine (11) , leucine (12) and threonine (13) in sepsis, for glutamine in endotoxaemia (10) , and for phenylalanine to support acutephase protein synthesis (14) . In other situations, combinations of AA have been proposed (10,15,16) . Obviously different stages of injury, infection or recover...

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Section: Discussionmentioning

confidence: 77%

Responses in whole-body amino acid kinetics to an acute, sub-clinical endotoxin challenge in lambs

et al. 2015

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“…In addition, oxidative stress leads to an increased Hcy flux through the transsulfuration pathway by up-regulation of CBS activity (35) and decreased activity of methionine synthase and betaine-Hcy S-methyltransferase (19)(20)(21). Increased transsulfuration rates during experimentally induced sepsis were also shown by injection of radiolabeled cysteine and methionine in rats (36,37).…”

Section: Discussionmentioning

confidence: 99%

Methionine metabolism in an animal model of sepsis

Semmler¹,

Smulders²,

Struys³

et al. 2008

Clinical Chemistry and Laboratory Medicine

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Background: Sepsis is a disease with high incidence and lethality and is accompanied by profound metabolic disturbances. In mammalian methionine metabolism, S-adenosylmethionine (SAM) is produced, which is important in the synthesis of neurotransmitters and glutathione and as an anti-inflammatory agent. The degradation product and antagonist of SAM is S-adenosylhomocysteine (SAH). In this study, we investigated changes in methionine metabolism in a rodent model of sepsis. Methods: Sepsis was induced in male Wistar rats (ns21) by intraperitoneal injection of bacterial lipopolysaccharide (10 mg/kg). Controls (ns18) received vehicle only. Blood was collected by cardiac puncture 24 h later. Puncture of the suboccipital fossa was performed to collect cerebrospinal fluid (CSF). Methionine metabolites were measured using stable isotope dilution tandem mass spectrometry. Plasma total homocysteine and cysteine were measured by HPLC using fluorescence detection. Glutathione was assayed using a modified enzymatic microtiter plate assay. Results: We observed significantly higher plasma levels of SAM (p-0.001) and SAM/SAH ratio (ps0.004) in septic animals. In CSF, there was also a trend for higher levels of SAM in septic animals (ps0.067). Oxidative stress was reflected by an increase in the ratio of oxidized/reduced glutathione in septic animals (ps0.001). Conclusions: Sepsis is associated with an increase in SAM/SAH ratio in plasma and CSF in rodents. This indicates an altered methylation potential during sepsis, which may be relevant for sepsis-associated

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“…Secondly, microarray transcriptome analysis reveals that transcript levels of genes required for cysteine synthesis, the yrrT operon and cysK, increase when Spx interacts with RNAP (34). The stimulation of homocysteine production and transsulfuration is characteristic of cells responding to oxidative stress (4,12,21,28,29,37,39,47). In mammalian systems, cysteine production is accelerated during bacterial infection because of an increased need for glutathione.…”

Section: Discussionmentioning

confidence: 99%

The Global Regulator Spx Functions in the Control of Organosulfur Metabolism inBacillus subtilis

et al. 2006

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Spx is a global transcriptional regulator of the oxidative stress response in Bacillus subtilis. Its target is RNA polymerase, where it contacts the ␣ subunit C-terminal domain. Recently, evidence was presented that Spx participates in sulfate-dependent control of organosulfur utilization operons, including the ytmI, yxeI, ssu, and yrrT operons. The yrrT operon includes the genes that function in cysteine synthesis from S-adenosylmethionine through intermediates S-adenosylhomocysteine, ribosylhomocysteine, homocysteine, and cystathionine. These operons are also negatively controlled by CymR, the repressor of cysteine biosynthesis operons. All of the operons are repressed in media containing cysteine or sulfate but are derepressed in medium containing the alternative sulfur source, methionine. Spx was found to negatively control the expression of these operons in sulfate medium, in part, by stimulating the expression of the cymR gene. In addition, microarray analysis, monitoring of yrrT-lacZ fusion expression, and in vitro transcription studies indicate that Spx directly activates yrrT operon expression during growth in medium containing methionine as sole sulfur source. These experiments have uncovered additional roles for Spx in the control of gene expression during unperturbed, steadystate growth.The global regulator Spx of Bacillus subtilis functions in the oxidative stress response by activating transcription of genes that function in thiol homeostasis (33,34,49). In this capacity, it is required for the transcriptional activation of the thioredoxin (trxA) and thioredoxin reductase (trxB) genes in response to disulfide stress. It also represses genes that function in a variety of metabolic and developmental pathways (34,35). The activity and synthesis of Spx are stimulated when cells undergo accelerated disulfide generation resulting from encounters with toxic oxidants. The accumulated Spx interacts with RNA polymerase (RNAP) in part by contacting residues of the alpha subunit C-terminal domain (CTD), while showing no sequence-specific DNA-binding activity (36). An important feature of Spx is the N-terminal CxxC redox disulfide motif that controls Spx activity. Transcriptional activation from the trxA and trxB promoters requires that the two cysteines be in the oxidized, disulfide state. The presence of a reductant that converts the cysteines to the thiol state results in loss of transcription-stimulating activity (33). It is currently not known how the interaction of oxidized Spx protein with RNA polymerase activates transcription at promoters under Spx positive control.In addition to its role in oxidative stress, recent studies indicate that Spx functions as a regulator of gene expression in cells undergoing steady-state growth. Spx was found to negatively affect the transcription of genes that function in the utilization of organosulfur compounds as alternative sources of sulfur (13). Such operons are repressed in minimal glucose media containing either of the two preferred sulfur sources, sulfate and cys...

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Methionine transsulfuration is increased during sepsis in rats

Cited by 68 publications

References 37 publications

Responses in whole-body amino acid kinetics to an acute, sub-clinical endotoxin challenge in lambs

Responses in whole-body amino acid kinetics to an acute, sub-clinical endotoxin challenge in lambs

Methionine metabolism in an animal model of sepsis

The Global Regulator Spx Functions in the Control of Organosulfur Metabolism inBacillus subtilis

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