Plasma concentrations of amino acid and nicotinamide metabolites in rheumatoid arthritis – potential biomarkers of disease activity and drug treatment

Smoleńska, Żaneta; Smolenski, Ryszard T.; Zdrojewski, Zbigniew

doi:10.3109/1354750x.2015.1130746

Cited by 37 publications

(29 citation statements)

References 14 publications

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“…Amino acid profiling and metabolome analysis using mass spectrometry have been powerful analytical tools [ 7 ] for revealed associations between plasma amino acid profiles and various diseases, including cancer [ 8 – 10 ], obesity and glucose metabolism [ 11 – 14 ], end-stage liver disease [ 15 ], inflammatory bowel disease [ 16 ], depression [ 17 ], rheumatoid arthritis [ 18 ], acute dissecting aortic aneurysm [ 19 ], and aging and longevity [ 20 , 21 ]. Understanding changes in amino acid profiles may therefore be useful for early diagnosis and insight into the pathophysiological mechanisms underlying such diseases.…”

Section: Introductionmentioning

confidence: 99%

Increased plasma proline concentrations are associated with sarcopenia in the elderly

et al. 2017

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Background and purposeMetabolome analyses have shown that plasma amino acid profiles reflect various pathological conditions, such as cancer and diabetes mellitus. It remains unclear, however, whether plasma amino acid profiles change in patients with sarcopenia. This study therefore aimed to investigate whether sarcopenia-specific changes occur in plasma amino acid profiles.MethodsA total of 153 community-dwelling and seven institutionalized elderly individuals (56 men, 104 women; mean age, 77.7±7.0 years) were recruited for this cross-sectional analysis. We performed a comprehensive geriatric assessment, which included an evaluation of hand grip strength, gait speed, muscle mass and blood chemistry, including the concentration of 18 amino acids.ResultsTwenty-eight of the 160 participants met the criteria for sarcopenia established by the Asian Working Group on Sarcopenia in Older People. Univariate analysis revealed associations between the presence of sarcopenia and a higher plasma concentration of proline and glutamine, lower concentrations of histidine and tryptophan. Multivariable analysis revealed that a higher concentration of proline was the only variable independently associated with sarcopenia.ConclusionsThe plasma concentration of proline may be useful for understanding the underlying pathophysiology of sarcopenia.

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Section: Introductionmentioning

confidence: 99%

Increased plasma proline concentrations are associated with sarcopenia in the elderly

et al. 2017

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“…Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by inflammation and joint damage with a heterogeneous course and different pathogenic mechanisms. 1 Chronic inflammation can lead to oxidative stress and consequently the formation of carbonyl, reactive carbonyl compounds, which are partly transformed into advanced glycation end products (AGEs). 2,3 Non-enzymatic glycation begins with interaction and link between the carbonyl group of a reducing sugar and an aminoterminal group of protein.…”

Section: Introductionmentioning

confidence: 99%

Increased serum concentrations of N^ɛ-carboxymethyllysine are related to the presence and the severity of rheumatoid arthritis

Knani

Bouzidi²,

Zrour

et al. 2017

Ann Clin Biochem

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Background There are limited data regarding the contribution of advanced glycation end products in the presence of rheumatoid arthritis. We investigated whether serum N-carboxymethyllysine and pentosidine were related to the presence and the severity of rheumatoid arthritis. Methods Eighty patients with rheumatoid arthritis and 30 control subjects were included in a cross-sectional study. The severity of rheumatoid arthritis was assessed using the disease activity score for 28 joints. Serum N-carboxymethyllysine and pentosidine were measured by enzyme-linked immunosorbent assay. Results Serum N-carboxymethyllysine and pentosidine concentrations were significantly higher in patients with rheumatoid arthritis vs. control subjects ( P < 0.001). Serum N-carboxymethyllysine and pentosidine concentrations were significantly higher in rheumatoid arthritis patients with high disease activity vs. rheumatoid arthritis patients with moderate disease activity ( P < 0.001, P = 0.019, respectively). A multiple logistic regression analysis demonstrated that N-carboxymethyllysine was independently associated with the presence of rheumatoid arthritis (OR = 1.21, 95% CI: 1.05-1.39, P = 0.006). Furthermore, in a multivariate stepwise regression analysis, N-carboxymethyllysine was independently correlated with disease activity score for 28 joints (standardized β = 0.43, P = 0.001). Conclusion Serum N-carboxymethyllysine and pentosidine were increased during rheumatoid arthritis, and N-carboxymethyllysine was independently associated with the presence and the severity of rheumatoid arthritis.

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“…In minimal medium containing 20% heat-inactivated serum, no differences in growth were observed in heat-inactivated serum between WT KPPR1 and KPPR1Δ gltA strains (Fig 5A and 5B), and these results were replicated in non-heat-inactivated serum (S7 Fig). To determine if amino acid levels in reported in human blood are sufficient to functionally complement the loss of gltA , we tested the growth of WT KPPR1 and KPPR1Δ gltA strains in minimal medium with serum-level concentrations of glutamine, glutamate, and proline [49,50], which are higher than those measured in BALF (Table 2). Indeed, serum-level concentrations of glutamine, glutamate, and proline were able to restore growth of the KPPR1Δ gltA strain (Fig 5C and 5D).…”

Section: Resultsmentioning

confidence: 99%

The Klebsiella pneumoniae citrate synthase gene, gltA, influences site specific fitness during infection

et al. 2019

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Klebsiella pneumoniae (Kp), one of the most common causes of healthcare-associated infections, increases patient morbidity, mortality, and hospitalization costs. Kp must acquire nutrients from the host for successful infection; however, the host is able to prevent bacterial nutrient acquisition through multiple systems. This includes the innate immune protein lipocalin 2 (Lcn2), which prevents Kp iron acquisition. To identify novel Lcn2-dependent Kp factors that mediate evasion of nutritional immunity during lung infection, we undertook an InSeq study using a pool of >20,000 transposon mutants administered to Lcn2 +/+ and Lcn2 -/- mice. Comparing transposon mutant frequencies between mouse genotypes, we identified the Kp citrate synthase, GltA, as potentially interacting with Lcn2, and this novel finding was independently validated. Interestingly, in vitro studies suggest that this interaction is not direct. Given that GltA is involved in oxidative metabolism, we screened the ability of this mutant to use a variety of carbon and nitrogen sources. The results indicated that the gltA mutant has a distinct amino acid auxotrophy rendering it reliant upon glutamate family amino acids for growth. Deletion of Lcn2 from the host leads to increased amino acid levels in bronchioloalveolar lavage fluid, corresponding to increased fitness of the gltA mutant in vivo and ex vivo . Accordingly, addition of glutamate family amino acids to Lcn2 +/+ bronchioloalveolar lavage fluid rescued growth of the gltA mutant. Using a variety of mouse models of infection, we show that GltA is an organ-specific fitness factor required for complete fitness in the spleen, liver, and gut, but dispensable in the bloodstream. Similar to bronchioloalveolar lavage fluid, addition of glutamate family amino acids to Lcn2 +/+ organ lysates was sufficient to rescue the loss of gltA . Together, this study describes a critical role for GltA in Kp infection and provides unique insight into how metabolic flexibility impacts bacterial fitness during infection.

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Plasma concentrations of amino acid and nicotinamide metabolites in rheumatoid arthritis – potential biomarkers of disease activity and drug treatment

Cited by 37 publications

References 14 publications

Increased plasma proline concentrations are associated with sarcopenia in the elderly

Increased plasma proline concentrations are associated with sarcopenia in the elderly

Increased serum concentrations of N^ɛ-carboxymethyllysine are related to the presence and the severity of rheumatoid arthritis

The Klebsiella pneumoniae citrate synthase gene, gltA, influences site specific fitness during infection

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Plasma concentrations of amino acid and nicotinamide metabolites in rheumatoid arthritis – potential biomarkers of disease activity and drug treatment

Cited by 37 publications

References 14 publications

Increased plasma proline concentrations are associated with sarcopenia in the elderly

Increased plasma proline concentrations are associated with sarcopenia in the elderly

Increased serum concentrations of Nɛ-carboxymethyllysine are related to the presence and the severity of rheumatoid arthritis

The Klebsiella pneumoniae citrate synthase gene, gltA, influences site specific fitness during infection

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Increased serum concentrations of N^ɛ-carboxymethyllysine are related to the presence and the severity of rheumatoid arthritis