Quantitative metabolomic analysis of the human cornea and aqueous humor

Snytnikova, Olga A.; Yanshole, Lyudmila V.; Iskakov, I. A.; Yanshole, Vadim V.; Черных, В. В.; Stepakov, Denis A.; Новоселов, В. П.; Tsentalovich, Yuri P.

doi:10.1007/s11306-017-1281-0

Cited by 35 publications

(35 citation statements)

References 32 publications

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“…The baseline processing and integration were done using the MestReNova v12.0 software. The metabolite signal assignment was confirmed by the addition of authentic compounds into samples and using the Human Metabolome Database [38,39] and our own experience in the metabolomic profiling of animal and human tissues and biofluids [37,[40][41][42][43]. The concentrations of metabolites in samples were calculated by the peak area integration respectively to the internal standard.…”

Section: Metabolite Extraction and Nmr Spectroscopymentioning

confidence: 99%

Fucose Ameliorates Tryptophan Metabolism and Behavioral Abnormalities in a Mouse Model of Chronic Colitis

et al. 2020

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Growing evidence suggests that intestinal mucosa homeostasis impacts immunity, metabolism, the Central Nervous System (CNS), and behavior. Here, we investigated the effect of the monosaccharide fucose on inflammation, metabolism, intestinal microbiota, and social behavior in the Dextran Sulfate Sodium (DSS)-induced chronic colitis mouse model. Our data show that chronic colitis is accompanied by the decrease of the serum tryptophan level and the depletion of the intestinal microbiota, specifically tryptophan-producing E. coli and Bifidobacterium. These changes are associated with defects in the male mouse social behavior such as a lack of preference towards female bedding in an odor preference test. The addition of fucose to the test animals' diet altered the bacterial community, increased the abundance of tryptophan-producing E. coli, normalized blood tryptophan levels, and ameliorated social behavior deficits. At the same time, we observed no ameliorating effect of fucose on colon morphology and colitis. Our results suggest a possible mechanism by which intestinal inflammation affects social behavior in male mice. We propose fucose as a promising prebiotic, since it creates a favorable environment for the beneficial bacteria that promote normalization of serum tryptophan level and amelioration of the behavioral abnormalities in the odor preference test.

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Section: Metabolite Extraction and Nmr Spectroscopymentioning

confidence: 99%

Fucose Ameliorates Tryptophan Metabolism and Behavioral Abnormalities in a Mouse Model of Chronic Colitis

et al. 2020

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“…1 H-NMR spectra of protein-free lipid-free extracts from heart and liver of R. amurensis were obtained for frogs exposed to extreme hypoxia (n = 6) and for control animals (n = 6). The signal assignment in the spectra was performed according to the metabolite NMR spectra available in literature and in our in-house library [46][47][48] . In questionable cases, signal attribution was confirmed by spiking the extract with commercial standard compounds.…”

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confidence: 99%

Metabolic response of the Siberian wood frog Rana amurensis to extreme hypoxia

Shekhovtsov

Булахова

Tsentalovich

et al. 2020

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the Siberian wood frog Rana amurensis is a recently discovered example of extreme hypoxia tolerance that is able to survive several months without oxygen. We studied metabolomic profiles of heart and liver of R. amurensis exposed to 17 days of extreme hypoxia. Without oxygen, the studied tissues experience considerable stress with a drastic decrease of ATP, phosphocreatine, and NAD+ concentrations, and concomitant increase of AMP, creatine, and NADH. Heart and liver switch to different pathways of glycolysis with differential accumulation of lactate, alanine, succinate, as well as 2,3-butanediol (previously not reported for vertebrates as an end product of glycolysis) and depletion of aspartate. We also observed statistically significant changes in concentrations of certain osmolytes and choline-related compounds. Low succinate/fumarate ratio and high glutathione levels indicate adaptations to reoxygenation stress. Our data suggest that maintenance of the ATP/ADP pool is not required for survival of R. amurensis, in contrast to anoxia-tolerant turtles. Anoxia is a huge stress for the majority of vertebrates. Amphibians are considered to be relatively anoxia-intolerant, in contrast to a few turtle species and certain fish species 1-3 : the most resistant species are known to survive anoxia for a few days at most. However, a recent study 4 proved that the Siberian wood frog Rana amurensis can tolerate almost complete anoxia at 2-3 °C (below 0.2 mg/L oxygen, i.e., less than 1.5% of the normal concentration at this temperature) for several months. This is on par with the best vertebrate models from other classes. Moreover, while red-eared slider turtles, the most studied anoxia-tolerant tetrapods, are dormant under anoxia, the Siberian wood frog is able to react to stimuli, e.g., to flee when disturbed. R. amurensis is thus a unique model of extreme hypoxia tolerance among terrestrial vertebrates. The natural range of R. amurensis includes Northeastern China and Siberia from the Urals to the coast of the Okhotsk sea; its northern distribution is limited by about 71° N. It overwinters under ice in water bodies. Many of these lakes are shallow (< 3 m) due to thermokarst origin, i.e. resulting from local melting of permafrost. Experimental studies 4 demonstrated that during the winter oxygen is depleted in overwintering sites till almost complete anoxia. Siberian wood frogs overwinter for 6 to 7 months in different regions under hypoxia until they can leave the lakes in April-early May. The mechanisms of adaptation to the lack of oxygen are totally unknown for R. amurensis. Here we made an attempt to study this phenomenon using 1 H-NMR-based quantitative metabolomics. This method simultaneously yields concentrations of multiple metabolites 5. At the present, the detailed quantitative metabolomic composition is known for many human tissues, but for very few animals 6-8. To the best of our knowledge, this is the first report on the quantitative metabolomic analysis of amphibian tissues. We determined concentrations of ove...

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“…Recent studies point to the metabolic changes as a key to understand the pathogenesis of eye diseases [17][18][19]. The pathologic processes occurring in corneal tissue can be reflected in the metabolome changes, causing the increase or decrease of particular metabolites [20]. Metabolomic indicators of oxidative stress, such as glutathione, are considered as one of the major factors involved in the development of corneal diseases [21].…”

Section: Introductionmentioning

confidence: 99%

“…In recent years several groups have investigated the metabolome composition of keratoconic cornea tissue [27] as well as the aqueous humor [28] and tear film of KC patients [20]. The metabolome composition of the human cornea has been studied with the use of different NMR spectroscopy techniques, including 31 P NMR [29] and HR-MAS 1 H NMR [27].…”

Section: Introductionmentioning

confidence: 99%

“…The metabolome composition of the human cornea has been studied with the use of different NMR spectroscopy techniques, including 31 P NMR [29] and HR-MAS 1 H NMR [27]. Mass spectrometry methods, mainly coupled to liquid chromatography (LC/MS), were applied for metabolomics studies of the human lens [30], tear fluid [21], or aqueous humor [20]. However, the knowledge of the metabolome composition of the human cornea in specific pathogenic conditions remains very limited.…”

Section: Introductionmentioning

confidence: 99%

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Metabolomic Signature Discriminates Normal Human Cornea from Keratoconus—A Pilot GC/MS Study

et al. 2020

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The molecular etiology of keratoconus (KC), a pathological condition of the human cornea, remains unclear. The aim of this work was to perform profiling of metabolites and identification of features discriminating this pathology from the normal cornea. The combination of gas chromatography and mass spectrometry (GC/MS) techniques has been applied for profiling and identification of metabolites in corneal buttons from 6 healthy controls and 7 KC patients. An untargeted GC/MS-based approach allowed the detection of 377 compounds, including 46 identified unique metabolites, whose levels enabled the separation of compared groups of samples in unsupervised hierarchical cluster analysis. There were 13 identified metabolites whose levels differentiated between groups of samples. Downregulation of several carboxylic acids, fatty acids, and steroids was observed in KC when compared to the normal cornea. Metabolic pathways associated with compounds that discriminated both groups were involved in energy production, lipid metabolism, and amino acid metabolism. An observed signature may reflect cellular processes involved in the development of KC pathology, including oxidative stress and inflammation.

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Quantitative metabolomic analysis of the human cornea and aqueous humor

Cited by 35 publications

References 32 publications

Fucose Ameliorates Tryptophan Metabolism and Behavioral Abnormalities in a Mouse Model of Chronic Colitis

Fucose Ameliorates Tryptophan Metabolism and Behavioral Abnormalities in a Mouse Model of Chronic Colitis

Metabolic response of the Siberian wood frog Rana amurensis to extreme hypoxia

Metabolomic Signature Discriminates Normal Human Cornea from Keratoconus—A Pilot GC/MS Study

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