GC/TOF-MS-based metabolomic profiling in cultured fibroblast-like synoviocytes from rheumatoid arthritis

Ahn, Joong Kyong; Kim, Sooah; Hwang, Jiwon; Kim, Jungyeon; Kim, Kyoung Heon; Suk, Hoon

doi:10.1016/j.jbspin.2015.11.009

Cited by 68 publications

(53 citation statements)

References 40 publications

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“…Metabolomics profiling has shown alterations in the lipid metabolism in RA versus OA FLS. In line with this evidence, choline and choline like transporter (CTL)1 (high-affinity) and CTL2 (low affinity), were found to be highly expressed by synovial RA FLS (Ahn et al, 2016;Volchenkov et al, 2017) and their functional inhibition promoted FLS cell death (Seki et al, 2017). Supporting these findings, positron emission tomography (PET) scanning with 11 C-choline showed increased uptake in inflamed arthritic joints (Seki et al, 2017).…”

Section: Lipid Metabolismmentioning

confidence: 56%

Metabolic Checkpoints in Rheumatoid Arthritis

et al. 2020

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Several studies have highlighted the interplay between metabolism, immunity and inflammation. Both tissue resident and infiltrating immune cells play a major role in the inflammatory process of rheumatoid arthritis (RA) via the production of cytokines, adipocytokines and metabolic intermediates. These functions are metabolically demanding and require the most efficient use of bioenergetic pathways. The synovial membrane is the primary site of inflammation in RA and exhibits distinctive histological patterns characterized by different metabolism, prognosis and response to treatment. In the RA synovium, the high energy demand by stromal and infiltrating immune cells, causes the accumulation of metabolites, and adipo-cytokines, which carry out signaling functions, as well as activating transcription factors which act as metabolic sensors. These events drive immune and joint-resident cells to acquire pro-inflammatory effector functions which in turn perpetuate chronic inflammation. Whether metabolic changes are a consequence of the disease or one of the causes of RA pathogenesis is still under investigation. This review covers our current knowledge of cell metabolism in RA. Understanding the intricate interactions between metabolic pathways and the inflammatory and immune responses will provide more awareness of the mechanisms underlying RA pathogenesis and will identify novel therapeutic options to treat this disease.

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Section: Lipid Metabolismmentioning

confidence: 56%

Metabolic Checkpoints in Rheumatoid Arthritis

et al. 2020

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“…The RA-associated environment is characterised by hypoxia and heterogeneous availability of nutrients, resembling that of some tumours (39). Our data suggest that in addition to contributing to the inflammatory state through production of antibodies against citrullinated proteins, PADI1 and PADI3 expression in RA and subsequent PKM2 citrullination may account for the increased glycolysis seen in activated RA-associated fibroblast-like synoviocytes, another hallmark of the disease (39)(40)(41).…”

Section: Excess Fbp Did However Counteract Inhibition Of Glycolysis Bmentioning

confidence: 72%

Citrullination of pyruvate kinase by PADI1 and PADI3 regulates glycolysis and cancer cell proliferation

Davidson

Coassolo

Davidson

et al. 2019

Preprint

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CHD3 and CHD4 are mutually exclusive ATPase subunits of the Nucleosome Remodelling and Deacetylation (NuRD) complex that regulates gene expression. CHD4 is essential for growth of multiple patient derived melanoma xenografts and for breast cancer. Here we show that CHD4 regulates expression of PADI1 (Protein Arginine Deiminase 1) and PADI3 in multiple cancer cell types modulating citrullination of three arginines of the allostericallyregulated glycolytic enzyme pyruvate kinase M2 (PKM2). PKM2 citrullination lowers sensitivity to the inhibitors Tryptophan, Alanine and Phenylalanine shifting the equilibrium towards the activator Serine. Citrullination thus bypasses normal physiological regulation by low Serine levels to promote excessive glycolysis defining a novel pathway regulating proliferation of melanoma and other cancer cells. We provide unique insight as to how conversion of arginines to citrulline impacts key interactions within PKM2 reprogramming its activity as an additional layer of complexity to the mechanisms regulating this important enzyme.Significance. This study describes the mechanism by which citrullination of key arginines in pyruvate kinase M2 reprograms its allosteric regulation by the activating amino acid serine.PKM2 citrullination defines a novel pathway regulating glycolysis and cancer cell proliferation.3 Introduction.

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“…When we study the pathways in specific conditions like fever, age and involvement of joint movement, we show that tyrosine metabolism and phenylalanine metabolism are most affected. Dysregulation of Tyrosine metabolism has been reported with age and arthritic conditions3839. Involvement of these pathways in different infections like HIV has been previously reported4041.…”

Section: Discussionmentioning

confidence: 91%

Serum metabolomics analysis of patients with chikungunya and dengue mono/co-infections reveals distinct metabolite signatures in the three disease conditions

Shrinet

Shastri

Gaind

et al. 2016

Sci Rep

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Chikungunya and dengue are arboviral infections with overlapping clinical symptoms. A subset of chikungunya infection occurs also as co-infections with dengue, resulting in complications during diagnosis and patient management. The present study was undertaken to identify the global metabolome of patient sera infected with chikungunya as mono infections and with dengue as co-infections. Using nuclear magnetic resonance (NMR) spectroscopy, the metabolome of sera of three disease conditions, namely, chikungunya and dengue as mono-infections and when co-infected were ascertained and compared with healthy individuals. Further, the cohorts were analyzed on the basis of age, onset of fever and joint involvement. Here we show that many metabolites in the serum are significantly differentially regulated during chikungunya mono-infection as well as during chikungunya co-infection with dengue. We observed that glycine, serine, threonine, galactose and pyrimidine metabolisms are the most perturbed pathways in both mono and co-infection conditions. The affected pathways in our study correlate well with the clinical manifestation like fever, inflammation, energy deprivation and joint pain during the infections. These results may serve as a starting point for validations and identification of distinct biomolecules that could be exploited as biomarker candidates thereby helping in better patient management.

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GC/TOF-MS-based metabolomic profiling in cultured fibroblast-like synoviocytes from rheumatoid arthritis

Cited by 68 publications

References 40 publications

Metabolic Checkpoints in Rheumatoid Arthritis

Metabolic Checkpoints in Rheumatoid Arthritis

Citrullination of pyruvate kinase by PADI1 and PADI3 regulates glycolysis and cancer cell proliferation

Serum metabolomics analysis of patients with chikungunya and dengue mono/co-infections reveals distinct metabolite signatures in the three disease conditions

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