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- Lipidomics, Atrial Conduction, and Body Mass Index. [Journal Article]
- CGCirc Genom Precis Med 2019; 12(7):e002384
- CONCLUSIONS: Increased %PC 38:3 levels are consistently associated with longer PWD, partly because of the confounding effect of BMI. The causal effect of BMI on PWD reinforces evidence of BMI's involvement into atrial electrical activity.
- Alcoholic and non-alcoholic fatty liver disease: Focus on ceramide. [Review]
- ABAdv Biol Regul 2018; 70:40-50
- Sphingolipids are class of metabolically distinct lipids that play structural and signaling functions in all organisms. Sphingolipid metabolism is deregulated during various diseases such as cancer, …
Sphingolipids are class of metabolically distinct lipids that play structural and signaling functions in all organisms. Sphingolipid metabolism is deregulated during various diseases such as cancer, neurological and immune disorders, and metabolic syndrome. With the advancement of sphingo-lipidomics and sphingo-genomics, an understanding of the specific roles of ceramide, the quintessential bioactive sphingolipid, in fatty liver disease has taken shape. Two major pathways for ceramide generation, the de novo pathway and the sphingomyelinase pathway are activated in the course of both, the non-alcoholic and the alcoholic, forms of fatty liver disease. The mechanisms of activation of these two pathways are distinct and reflect the different disease etiology in each case; at the same time, common processes impacted by the resulting ceramide overproduction involve lipotoxocity, ER/mitochondrial stress, inflammation, and de-regulation of hepatic lipid metabolism. Studies in human patients and animal models have delineated specific enzymes and ceramide species that are involved at the different stages of the disease, and represent novel pharmaceutical targets for successful management of fatty liver disease.
- Biochemical changes in injured sciatic nerve of rats after low-level laser therapy (660 nm and 808 nm) evaluated by Raman spectroscopy. [Journal Article]
- LMLasers Med Sci 2019; 34(3):525-535
- The aim of this study was to identify biochemical changes in sciatic nerve (SN) after crush injury and low-level laser therapy (LLLT) with 660 nm and 808 nm by Raman spectroscopy (RS) analysis. A num…
The aim of this study was to identify biochemical changes in sciatic nerve (SN) after crush injury and low-level laser therapy (LLLT) with 660 nm and 808 nm by Raman spectroscopy (RS) analysis. A number of 32 Wistar rats were used, divided into four groups (control 1, control 2, LASER 660 nm, and LASER 808 nm). All animals underwent surgical procedure of the SN and groups control 2, LASER 660 nm, and LASER 808 nm were submitted to SN crush damage (axonotmesis). The LLLT in the groups LASER 660 nm and LASER 808 nm was applied daily for 21 consecutive days (100 mW, 30 s, 133 J/cm2 fluence). The hind paw was removed and the SN was dissected and positioned on an aluminum support to collect dispersive Raman spectra (830 nm excitation, 30 s accumulation). To estimate the biochemical changes in the SN associated with LLLT, the principal component analysis (PCA) was applied. The Raman spectra of the sciatic nerve fragments showed peaks of the major biochemical components of the nerve, especially sphingolipids, phospholipids, glycoproteins, and collagen. The spectral features identified in some of the principal component loading vectors are referred to the biochemical elements present on the SN and were increased in the groups treated with LLLT, mainly lipids (sphingo and phospholipids) and proteins (collagen)-constituents of the myelin sheath. The RS was effective in identifying the biochemical differences in the SN after the crush injury, and LASER 660 nm was more efficient than the LASER 808 nm in cell proliferation and repair of the injured SN.
- A Comparative Study of Human Saposins. [Journal Article]
- MMolecules 2018 Feb 14; 23(2)
- Saposins are small proteins implicated in trafficking and loading of lipids onto Cluster of Differentiation 1 (CD1) receptor proteins that in turn present lipid antigens to T cells and a variety of T…
Saposins are small proteins implicated in trafficking and loading of lipids onto Cluster of Differentiation 1 (CD1) receptor proteins that in turn present lipid antigens to T cells and a variety of T-cell receptors, thus playing a crucial role in innate and adaptive immune responses in humans. Despite their low sequence identity, the four types of human saposins share a similar folding pattern consisting of four helices linked by three conserved disulfide bridges. However, their lipid-binding abilities as well as their activities in extracting, transporting and loading onto CD1 molecules a variety of sphingo- and phospholipids in biological membranes display two striking characteristics: a strong pH-dependence and a structural change between a compact, closed conformation and an open conformation. In this work, we present a comparative computational study of structural, electrostatic, and dynamic features of human saposins based upon their available experimental structures. By means of structural alignments, surface analyses, calculation of pH-dependent protonation states, Poisson-Boltzmann electrostatic potentials, and molecular dynamics simulations at three pH values representative of biological media where saposins fulfill their function, our results shed light into their intrinsic features. The similarities and differences in this class of proteins depend on tiny variations of local structural details that allow saposins to be key players in triggering responses in the human immune system.
- Phytosphingosine is a novel activator of GPR120. [Journal Article]
- JBJ Biochem 2018 Jul 01; 164(1):27-32
- GPR120 is a receptor for long chain fatty acids and is expressed in small intestinal endocrine cells, L cells and adipose tissue. Activation of GPR120 promotes the secretion of incretin GLP-1, which …
GPR120 is a receptor for long chain fatty acids and is expressed in small intestinal endocrine cells, L cells and adipose tissue. Activation of GPR120 promotes the secretion of incretin GLP-1, which is known to have effects on anti-metabolic syndrome. As such, GPR120 is a potential target of pharmaceuticals for type II diabetes. In this study, we performed ligand-screening for GPR120 on glycero- and sphingo-type lipids and their derivatives using a Transforming Growth Factor α-shedding assay. We found that phytosphingosine (PHS) activates GPR120 in a manner comparable to the natural ligand α-linolenic acid (ALA) and superior to that of the synthetic ligand GW9508. The IC50 value of PHS was 33.4 μM, of ALA was 31.0 μM and of GW9508 was 41.7 μM. Additionally, PHS-induced activation of GPR120 was inhibited by the specific antagonist AH7614. Many of the natural or synthetic ligands found thus far are compounds with carboxyl groups. However, PHS does not possess a carboxyl group, suggesting that its manner of interaction with GPR120 may be significantly different from that of other ligands. Since PHS is rich in the plasma membrane of yeast, our results imply that PHS found in fermented food could have effects on anti-diabetes through activation of GPR120.
- Glyco-sphingo biology: a novel perspective for potential new treatments in Huntington's disease. [Journal Article]
- NRNeural Regen Res 2017; 12(9):1439-1440
- Comprehensive identification of sphingolipid species by in silico retention time and tandem mass spectral library. [Journal Article]
- JCJ Cheminform 2017; 9:19
- CONCLUSIONS: MS-DIAL and MS-FINDER software programs can identify 42 lipid classes (21 sphingo- and 21 glycerolipids) with the in silico RT and MS/MS library. The library is freely available as Microsoft Excel files at the software section of our RIKEN PRIMe website (http://prime.psc.riken.jp/).
- LONG–TERM FOOD RESTRICTION PREVENTS THE AGE-RELATED CHANGES OF THE CONTENT OF BIOLOGYCALLY ACTIVE SPHINGO- AND GLYCEROLIPIDS СONTENS IN THE RAT TISSUES. [Journal Article]
- FZFiziol Zh 2016; 62(2):103-9
- Age peculiarities of the calorie-restricted diet effects on the contents biologically active sphingo- and glycerolipids were studied in the heart, liver and brain of 3- and 24-month-old rats. Rats we…
Age peculiarities of the calorie-restricted diet effects on the contents biologically active sphingo- and glycerolipids were studied in the heart, liver and brain of 3- and 24-month-old rats. Rats were either kept on the ad libitum diet or on a calorie restricted diet (70-80% reduction in total calories) without reduction in essential nutrients. It has been determined that calorie restricted diet decreased the ceramide, sphingomyelin, cardiolipin and phosphatidic acid levels in the all investigated tissues of the rats. At the same time, calorie restriction diet prevented the age-induced ceramide and phosphatidic acid accumulation, ceramide/sphingomyelin ratio elevation, and sphingomyelin and cardiolipin content decrease in the tissues of 24-month-old rats. In addition, tissue specificity of calorierestricted diet effects has been determined. The Elevated levels of cardiolipin and phosphatidic acid were determined in the heart and liver of 24 months-old rats under calorie-restricted diet, in comparison to control animals, whereas in the brain the caloric restriction diet had the opposite effects. These results suggest that calorie-restricted diet may prevent the development of age-associated pathologies due to the modulation of biologically active lipid turnover in the old tissues.
- Systematic review regarding metabolic profiling for improved pathophysiological understanding of disease and outcome prediction in respiratory infections. [Review]
- RRRespir Res 2015 Oct 15; 16:125
- Metabolic profiling through targeted quantification of a predefined subset of metabolites, performed by mass spectrometric analytical techniques, allows detailed investigation of biological pathways …
Metabolic profiling through targeted quantification of a predefined subset of metabolites, performed by mass spectrometric analytical techniques, allows detailed investigation of biological pathways and thus may provide information about the interaction of different organic systems, ultimately improving understanding of disease risk and prognosis in a variety of diseases. Early risk assessment, in turn, may improve patient management in regard to cite-of-care decisions and treatment modalities. Within this review, we focus on the potential of metabolic profiling to improve our pathophysiological understanding of disease and management of patients. We focus thereby on lower respiratory tract infections (LRTI) including community-acquired pneumonia (CAP) and chronic obstructive pulmonary disease (COPD), an important disease responsible for high mortality, morbidity and costs worldwide. Observational data from numerous clinical and experimental studies have provided convincing data linking metabolic blood biomarkers such as lactate, glucose or cortisol to patient outcomes. Also, identified through metabolomic studies, novel innovative metabolic markers such as steroid hormones, biogenic amines, members of the oxidative status, sphingo- and glycerophospholipids, and trimethylamine-N-oxide (TMAO) have shown promising results. Since many uncertainties remain in predicting mortality in these patients, further prospective and retrospective observational studies are needed to uncover metabolic pathways responsible for mortality associated with LRTI. Improved understanding of outcome-specific metabolite signatures in LRTIs may optimize patient management strategies, provide potential new targets for future individual therapy, and thereby improve patients' chances for survival.
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- Sphingolipids contribute to acetic acid resistance in Zygosaccharomyces bailii. [Journal Article]
- BBBiotechnol Bioeng 2016; 113(4):744-53
- Lignocellulosic raw material plays a crucial role in the development of sustainable processes for the production of fuels and chemicals. Weak acids such as acetic acid and formic acid are troublesome…
Lignocellulosic raw material plays a crucial role in the development of sustainable processes for the production of fuels and chemicals. Weak acids such as acetic acid and formic acid are troublesome inhibitors restricting efficient microbial conversion of the biomass to desired products. To improve our understanding of weak acid inhibition and to identify engineering strategies to reduce acetic acid toxicity, the highly acetic-acid-tolerant yeast Zygosaccharomyces bailii was studied. The impact of acetic acid membrane permeability on acetic acid tolerance in Z. bailii was investigated with particular focus on how the previously demonstrated high sphingolipid content in the plasma membrane influences acetic acid tolerance and membrane permeability. Through molecular dynamics simulations, we concluded that membranes with a high content of sphingolipids are thicker and more dense, increasing the free energy barrier for the permeation of acetic acid through the membrane. Z. bailii cultured with the drug myriocin, known to decrease cellular sphingo-lipid levels, exhibited significant growth inhibition in the presence of acetic acid, while growth in medium without acetic acid was unaffected by the myriocin addition. Furthermore, following an acetic acid pulse, the intracellular pH decreased more in myriocin-treated cells than in control cells. This indicates a higher inflow rate of acetic acid and confirms that the reduction in growth of cells cultured with myriocin in the medium with acetic acid was due to an increase in membrane permeability, thereby demonstrating the importance of a high fraction of sphingolipids in the membrane of Z. bailii to facilitate acetic acid resistance; a property potentially transferable to desired production organisms suffering from weak acid stress.