Characterization of anti-inflammatory compounds using transcriptomics, proteomics, and metabolomics in combination with multivariate data analysis

Verhoeckx, Kitty; Bijlsma, Sabina; Jespersen, Sonja; Ramaker, Raymond; Verheij, Elwin; Witkamp, Renger F.; Greef, J. van der; Rodenburg, Richard J.

doi:10.1016/j.intimp.2004.07.008

Cited by 67 publications

(51 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…55) Results from 1 H NMR metabolomics are also in agreement with those from in vivo 31 P NMR and HPLC-UV, in which phosphocreatine utilization for compensation of ATP loss could be used as an indicator of medaka embryotoxicity. 56) Medaka embryos were also used to construct developmental metabolic trajectories 40) and to understand the metabolic changes during normal embryogenesis as well as trichloroethylene-induced metabolic perturbation during embryogenesis.…”

Section: )supporting

confidence: 65%

“…LC-MS or LC-TOF MS (time-of-flight mass spectrometry) derived metabolic fingerprints, in association with statistical analysis, have been applied in the field of pharmacology and toxicology. [29][30][31] In studies of xenobiotics, a metabolomic approach can provide not only information on their biochemical effects in organisms, but also on their biotransformation pathways. The recent development of ultra performance liquid chromatography (UPLC) has resulted in a greater sensitivity and resolution compared to HPLC.…”

Section: Ms Techniquesmentioning

confidence: 99%

See 1 more Smart Citation

Metabolomics: Methodologies and applications in the environmental sciences

Lin¹,

Viant

Tjeerdema³

2006

J. Pestic. Sci.

176

View full text Add to dashboard Cite

Environmental metabolomics is an emerging approach for examining metabolic fingerprints, or profiles, in biological systems exposed to environmental stress. In conjunction with other "omics" techniques, such as genomics, transcriptomics, and proteomics, it has been used to study the biochemical impacts of xenobiotics and disease. The approach analyzes changes in the concentrations of metabolites, which are the precursors and products of enzymatic activity, and then attempts to associate these changes with biological function and/or regulation. Environmental scientists have recently applied such techniques to suggest biomarkers for the risk assessment of chemicals and for diagnosing diseases in wild animals. Furthermore, this approach can in principle allow scientists to better understand the underlying mechanisms of action of toxic compounds in the environment. In this review the methodologies used in metabolomics are briefly discussed along with several examples from the environmental sciences, including biomarker development and risk assessment of toxicant exposure, metabolic responses to environmental stressors, and disease diagnosis and monitoring.

show abstract

Section: )supporting

confidence: 65%

Section: Ms Techniquesmentioning

confidence: 99%

Metabolomics: Methodologies and applications in the environmental sciences

Lin¹,

Viant

Tjeerdema³

2006

J. Pestic. Sci.

176

View full text Add to dashboard Cite

show abstract

“…Since C. longa extract may block Gsa-protein activity rather than H 2 R, we tested the involvement of Gsa-protein in the activity of C. longa extract by treating the U937 cells with isoproterenol (500 nM), an agonist of the Gsa-protein coupled b 2 -adrenoceptor, following treatment with C. longa extract. 19,20) C. longa did not affect isoproterenol-induced cAMP production (Fig. 2B, closed box), indicating that the inhibitory effect of C. longa extract on the dimaprit-induced cAMP generation was through direct inhibition of H 2 R. We could not detect significant cellular damage (by MTT assay) in cells treated with vehicle or pretreated with ranitidine or C. longa extract (data not shown), suggesting that the C. longa inhibition of dimaprit-induced cAMP responses was not due to cell death.…”

Section: Effect Of C Longa On Gastric Acid Secretion and The Formatimentioning

confidence: 99%

Curcuma longa Extract Protects against Gastric Ulcers by Blocking H2 Histamine Receptors

Kim

Choi

et al. 2005

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

show abstract

“…The ␥-glutamyl-cysteine synthetase (Gsh1) 1 is considered as the ratelimiting enzyme of the GSH pathway since the homologous mammalian enzyme is inhibited in vitro by high levels of GSH (9), the end product of the pathway. Accordingly, previous work supports this notion in yeast (10), but no definitive proof has been provided, and this question remains opened.Generally, studies based on proteomic and gene expression profiling are interpreted in terms of cell metabolism, assuming a trivial link between protein expression and metabolic states, but few combined transcriptome, proteome, and metabolome studies (2,(11)(12)(13)(14) have been made to experimentally test these assumptions. The present study is intended to address the question of the correlation of metabolic data with the wealth of proteomic, genomic, and regulatory data currently available on one of the best investigated metabolic pathways.…”

mentioning

confidence: 99%

Combined Proteome and Metabolite-profiling Analyses Reveal Surprising Insights into Yeast Sulfur Metabolism

Lafaye

Junot

Pereira

et al. 2005

Journal of Biological Chemistry

118

View full text Add to dashboard Cite

Metabolomics is considered as an emerging new tool for functional proteomics in the identification of new protein function or in projects aiming at modeling whole cell metabolism. When combined with proteome studies, metabolite-profiling analyses revealed unanticipated insights into the yeast sulfur pathway. In response to cadmium, the observed overproduction of glutathione, essential for the detoxification of the metal, can be entirely accounted for by a marked drop in sulfur-containing protein synthesis and a redirection of sulfur metabolite fluxes to the glutathione pathway. A kinetic analysis showed sequential and dramatic changes in intermediate sulfur metabolite pools within the first hours of the treatment. Strikingly, whereas proteome and metabolic data were positively correlated under cadmium conditions, proteome and metabolic data were negatively correlated during other growth conditions, i.e. methionine supplementation or sulfate starvation. These differences can be explained by alternative mechanisms in the regulation of Met4, the activator of the sulfur pathway. Whereas Met4 activity is controlled by the cellular cysteine content in response to sulfur source and availability, the present study suggests that Met4 activation under cadmium conditions is cysteine-independent. The results clearly indicate that the metabolic state of a cell cannot be safely predicted based solely on proteomic and/or gene expression data. Combined metabolome and proteome studies are necessary to draw a comprehensive and integrated view of cell metabolism.Assimilable sulfur is essential for all living organisms. The cell requirement for sulfur can be fulfilled by the uptake of sulfur-containing amino acids or by assimilation of inorganic sulfur into organic compounds such as cysteine or homocysteine (1, 2). In yeast, homocysteine is the precursor of methionine through the methyl cycle and of cysteine through the transsulfuration pathway ( Fig. 1) (3). Cysteine is the sensor of the metabolic state in the sulfur amino acid pathway (4) and is required for the synthesis of GSH, an essential antioxidant molecule also important for detoxification.The yeast sulfur pathway has been extensively investigated at the genetic, enzymatic, and regulatory levels (3). The pools of most metabolites of the pathway have been analyzed (5, 6), and the K m values of many enzymes have been measured (3). However, some metabolic data such as the metabolite fluxes in the pathway and the concentration of the metabolites of the transsulfuration pathway (homocysteine and cystathionine) are lacking. Moreover, the levels of some sulfur metabolites are presumed to be modified in different mutants and under different physiological conditions (i.e. sulfur starvation, the presence of a sulfur metabolite, or a toxic metal in the medium), but the few quantitative data that are available are restricted to a small part of the pathway (5). Thus, it has been shown that cadmium (Cd 2ϩ ) strongly increases GSH synthesis (7), which is consistent with the primary impor...

show abstract

Characterization of anti-inflammatory compounds using transcriptomics, proteomics, and metabolomics in combination with multivariate data analysis

Cited by 67 publications

References 32 publications

Metabolomics: Methodologies and applications in the environmental sciences

Metabolomics: Methodologies and applications in the environmental sciences

Curcuma longa Extract Protects against Gastric Ulcers by Blocking H2 Histamine Receptors

Combined Proteome and Metabolite-profiling Analyses Reveal Surprising Insights into Yeast Sulfur Metabolism

Contact Info

Product

Resources

About