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1.
Poult Sci ; 99(2): 893-905, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32036985

RESUMO

Myo-inositol (MI) has gained relevance in physiology research during the last decade. As a constituent of animal cells, MI was proven to be crucial in several metabolic and regulatory processes. Myo-inositol is involved in lipid signaling, osmolarity, glucose, and insulin metabolism. In humans and rodents, dietary MI was assessed to be important for health so that MI supplementation appeared to be a valuable alternative for treatment of several diseases as well as for improvements in metabolic performance. In poultry, there is a lack of evidence not only related to specific species-linked metabolic processes but also about the effects of dietary MI on performance and health. This review intends to provide information about the meaning of dietary MI in animal metabolism as well as to discuss potential implications of dietary MI in poultry health and performance with the aim to identify open questions in poultry research.


Assuntos
Inositol/metabolismo , Aves Domésticas/metabolismo , Ração Animal/análise , Fenômenos Fisiológicos da Nutrição Animal , Animais , Dieta/veterinária , Inositol/química
2.
Biosci Biotechnol Biochem ; 84(4): 734-742, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31842701

RESUMO

scyllo-inositol dehydrogenase, isolated from Paracoccus laeviglucosivorans (Pl-sIDH), exhibits a broad substrate specificity: it oxidizes scyllo- and myo-inositols as well as L-glucose, converting L-glucose to L-glucono-1,5-lactone. Based on the crystal structures previously reported, Arg178 residue, located at the entry port of the catalytic site, seemed to be important for accepting substrates. Here, we report the role of Arg178 by using an alanine-substituted mutant for kinetic analysis as well as to determine the crystal structures. The wild-type Pl-sIDH exhibits the activity for scyllo-inositol most preferably followed by myo-inositol and L-glucose. On the contrary, the R178A mutant abolished the activities for both inositols, but remained active for L-glucose to the same extent as its wild-type. Based on the crystal structures of the mutant, the side chain of Asp191 flipped out of the substrate binding site. Therefore, Arg178 is important in positioning Asp191 correctly to exert its catalytic activities.Abbreviations: IDH: inositol dehydrogenase; LB: Luria-Bertani; kcat: catalyst rate constant; Km: Michaelis constant; NAD: nicotinamide dinucleotide; NADH: nicotinamide dinucleotide reduced form; PDB; Protein Data Bank; PDB entry: 6KTJ, 6KTK, 6KTL.


Assuntos
Substituição de Aminoácidos , Glucose/metabolismo , Inositol/metabolismo , Oxirredutases/metabolismo , Paracoccus/enzimologia , Cinética , Oxirredutases/isolamento & purificação , Conformação Proteica , Especificidade por Substrato
3.
Am J Physiol Endocrinol Metab ; 318(2): E237-E248, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-31874063

RESUMO

Polycystic ovary syndrome (PCOS) is an endocrine-metabolic disorder characterized by hyperandrogenism and ovulatory dysfunction but also obesity and hyperinsulinemia. These characteristics induce an insulin-resistant state in tissues such as the endometrium, affecting its reproductive functions. Myo-inositol (MYO) is an insulin-sensitizing compound used in PCOS patients; however, its insulin-sensitizing mechanism is unclear. To understand the relationship of MYO with insulin action in endometrial cells, sodium/myo-inositol transporter 1 (SMIT-1) (MYO-transporter), and MYO effects on protein levels related to the insulin pathway were evaluated. SMIT-1 was assessed in endometrial tissue from women with normal weight, obesity, insulin resistance, and PCOS; additionally, using an in vitro model of human endometrial cells exposed to an environment resembling hyperinsulinemic-obese-PCOS, MYO effect was evaluated on p-AMPK and GLUT-4 levels and glucose uptake by Western blot, immunocytochemistry, and confocal microscopy, respectively. SMIT-1 was detected in endometrial tissue from all groups and decreased in PCOS and obesity (P < 0.05 vs. normal weight). In the in vitro model, PCOS conditions decreased p-AMPK levels, while they were restored with MYO (P < 0.05). The diminished GLUT-4 protein levels promoted by PCOS environment were restored by MYO through SMIT-1 and p-AMPK-dependent mechanism (P < 0.05). Also, MYO restored glucose uptake in cells under PCOS condition through a p-AMPK-dependent mechanism. Finally, these results were similar to those obtained with metformin treatment in the same in vitro conditions. Consequently, MYO could be a potential insulin sensitizer through its positive effects on insulin-resistant tissues as PCOS-endometrium, acting through SMIT-1, provoking AMPK activation and elevated GLUT-4 levels and, consequently, increase glucose uptake by human endometrial cells. Therefore, MYO may be used as an effective treatment option in insulin-resistant PCOS women.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Endométrio/metabolismo , Transportador de Glucose Tipo 4/biossíntese , Inositol/metabolismo , Resistência à Insulina , Síndrome do Ovário Policístico/metabolismo , Adulto , Células Cultivadas , Endométrio/citologia , Ativação Enzimática , Feminino , Glucose/metabolismo , Transportador de Glucose Tipo 4/genética , Proteínas de Choque Térmico/metabolismo , Humanos , Hipoglicemiantes/farmacologia , Metformina/farmacologia , Obesidade/metabolismo , Síndrome do Ovário Policístico/genética , Simportadores/metabolismo
4.
J Chem Ecol ; 45(11-12): 926-933, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31758292

RESUMO

Chemical examination of plant constituents responsible for oviposition by a Magnoliaceae-feeding butterfly, Graphium doson, was conducted using its major host plant, Michelia compressa. A methanol extract prepared from young leaves of the plant elicited a strong oviposition response from females. The methanolic extract was then separated by solvent partition into three fractions: CHCl3, i-BuOH, and aqueous fractions. Active substance(s) resided in both i-BuOH- and water-soluble fractions. Bioassay-guided further fractionation of the water-soluble substances by means of various chromatographic techniques led to the isolation of an oviposition stimulant. The stimulant was identified as D-(+)-pinitol on the basis of 13C NMR spectra and physicochemical properties. D-(+)-Pinitol singly exhibited a moderate oviposition-stimulatory activity at a dose of 150 µg/cm2. This compound was present also in another host plant, Magnolia grandiflora, in a sufficient amount to induce oviposition behavior of G. doson females. Certain cyclitols including D-(+)-pinitol have been reported to be involved in stimulation of oviposition by some Aristolochiaceae- and Rutaceae-feeding papilionid butterflies. A possible pathway of phytochemical-mediated host shifts in the Papilionidae, in which certain cyclitols could enact important mediators, is discussed in relation to the evolution of cyclitol biosynthesis in plants.


Assuntos
Magnolia/química , Oviposição/efeitos dos fármacos , Extratos Vegetais/química , Animais , Butanóis/química , Borboletas , Ciclitóis/química , Ciclitóis/metabolismo , Feminino , Especificidade de Hospedeiro , Interações Hospedeiro-Parasita , Inositol/análogos & derivados , Inositol/química , Inositol/metabolismo , Magnolia/metabolismo , Extratos Vegetais/metabolismo , Folhas de Planta/química , Folhas de Planta/metabolismo , Solubilidade , Água/química
5.
Microb Cell Fact ; 18(1): 182, 2019 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-31655587

RESUMO

BACKGROUND: Oxidative stress caused by inevitable hostile conditions during fermentative process was the most serious threat to the survival of the well-known industrial microorganism Corynebacterium glutamicum. To survive, C. glutamicum developed several antioxidant defenses including millimolar concentrations of mycothiol (MSH) and protective enzymes. Glutathione (GSH) S-transferases (GSTs) with essentially defensive role in oxidative stress have been well defined in numerous microorganisms, while their physiological and biochemical functions remained elusive in C. glutamicum thus far. RESULTS: In the present study, we described protein NCgl1216 belonging to a novel MSH S-transferase Xi class (MstX), considered as the equivalent of GST Xi class (GSTX). MstX had a characteristic conserved catalytic motif (Cys-Pro-Trp-Ala, C-P-W-A). MstX was active as thiol transferase, dehydroascorbate reductase, mycothiolyl-hydroquinone reductase and MSH peroxidase, while it showed null activity toward canonical GSTs substrate as 1-chloro-2,4-dinitrobenzene (CDNB) and GST Omega's specific substance glutathionyl-acetophenones, indicating MstX had some biochemical characteristics related with mycoredoxin (Mrx). Site-directed mutagenesis showed that, among the two cysteine residues of the molecule, only the residue at position 67 was required for the activity. Moreover, the residues adjacent to the active Cys67 were also important for activity. These results indicated that the thiol transferase of MstX operated through a monothiol mechanism. In addition, we found MstX played important role in various stress resistance. The lack of C. glutamicum mstX gene resulted in significant growth inhibition and increased sensitivity under adverse stress condition. The mstX expression was induced by stress. CONCLUSION: Corynebacterium glutamicum MstX might be critically involved in response to oxidative conditions, thereby giving new insight in how C. glutamicum survived oxidative stressful conditions.


Assuntos
Proteínas de Bactérias/química , Corynebacterium glutamicum/metabolismo , Cisteína/metabolismo , Glutationa Transferase/química , Glicopeptídeos/metabolismo , Inositol/metabolismo , Oxirredução , Estresse Oxidativo
6.
J Biochem ; 166(5): 441-448, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31504617

RESUMO

Glycosylinositol phosphoceramide (GIPC) is the most abundant sphingolipid in plants and fungi. Recently, we detected GIPC-specific phospholipase D (GIPC-PLD) activity in plants. Here, we found that GIPC-PLD activity in young cabbage leaves catalyzes transphosphatidylation. The available alcohol for this reaction is a primary alcohol with a chain length below C4. Neither secondary alcohol, tertiary alcohol, choline, serine nor glycerol serves as an acceptor for transphosphatidylation of GIPC-PLD. We also found that cabbage GIPC-PLD prefers GIPC containing two sugars. Neither inositol phosphoceramide, mannosylinositol phosphoceramide nor GIPC with three sugar chains served as substrate. GIPC-PLD will become a useful catalyst for modification of polar head group of sphingophospholipid.


Assuntos
Biocatálise , Brassica/enzimologia , Ceramidas/metabolismo , Inositol/metabolismo , Fosfatidilcolinas/metabolismo , Fosfolipase D/metabolismo , Folhas de Planta/enzimologia , Brassica/química , Ceramidas/química , Inositol/análogos & derivados , Inositol/química , Estrutura Molecular , Fosfatidilcolinas/química , Fosfolipase D/química , Folhas de Planta/química
7.
Int J Mol Sci ; 20(16)2019 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-31426386

RESUMO

Inositol signaling is believed to play a crucial role in various aspects of plant growth and adaptation. As an important component in biosynthesis and degradation of myo-inositol and its derivatives, inositol phosphatases could hydrolyze the phosphate of the inositol ring, thus affecting inositol signaling. Until now, more than 30 members of inositol phosphatases have been identified in plants, which are classified intofive families, including inositol polyphosphate 5-phosphatases (5PTases), suppressor of actin (SAC) phosphatases, SAL1 phosphatases, inositol monophosphatase (IMP), and phosphatase and tensin homologue deleted on chromosome 10 (PTEN)-related phosphatases. The current knowledge was revised here in relation to their substrates and function in response to abiotic stress. The potential mechanisms were also concluded with the focus on their activities of inositol phosphatases. The general working model might be that inositol phosphatases would degrade the Ins(1,4,5)P3 or phosphoinositides, subsequently resulting in altering Ca2+ release, abscisic acid (ABA) signaling, vesicle trafficking or other cellular processes.


Assuntos
Inositol/metabolismo , Monoéster Fosfórico Hidrolases/metabolismo , Proteínas de Plantas/metabolismo , Plantas/metabolismo , Transdução de Sinais , Aclimatação , Inositol Polifosfato 5-Fosfatases/metabolismo , Fosfatidilinositóis/metabolismo , Fenômenos Fisiológicos Vegetais , Estresse Fisiológico
8.
Neurology ; 93(8): e758-e765, 2019 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-31315971

RESUMO

OBJECTIVE: To determine the frontal lobe proton magnetic resonance spectroscopy (1H MRS) abnormalities in asymptomatic and symptomatic carriers of microtubule-associated protein tau (MAPT) mutations. METHODS: We recruited patients with MAPT mutations from 5 individual families, who underwent single voxel 1H MRS from the medial frontal lobe at 3T (n = 19) from the Longitudinal Evaluation of Familial Frontotemporal Dementia Subjects (LEFFTDS) Study at the Mayo Clinic site. Asymptomatic MAPT mutation carriers (n = 9) had Frontotemporal Lobar Degeneration Clinical Dementia Rating Sum of Boxes (FTLD-CDR SOB) score of zero, and symptomatic MAPT mutation carriers (n = 10) had a median FTLD-CDR SOB score of 5. Noncarriers from healthy first-degree relatives of the patients were recruited as controls (n = 25). The demographic aspects and 1H MRS metabolite ratios were compared by use of the Fisher exact test for sex and linear mixed models to account for within-family correlations. We used Tukey contrasts for pair-wise comparisons. RESULTS: Asymptomatic MAPT mutation carriers had lower neuronal marker N-acetylaspartate (NAA)/creatine (Cr) (p = 0.001) and lower NAA/myo-inositol (mI) (p = 0.026) than noncarriers after adjustment for age. Symptomatic MAPT mutation carriers had lower NAA/Cr (p = 0.01) and NAA/mI (p = 0.01) and higher mI/Cr (p = 0.02) compared to noncarriers after adjustment for age. Furthermore, NAA/Cr (p = 0.006) and NAA/mI (p < 0.001) ratios decreased, accompanied by an increase in mI/Cr ratio (p = 0.001), as the ages of carriers approached and passed the age at symptom onset. CONCLUSION: Frontal lobe neurochemical alterations measured with 1H MRS precede the symptom onset in MAPT mutation carriers. Frontal lobe 1H MRS is a potential biomarker for early neurodegenerative processes in MAPT mutation carriers.


Assuntos
Ácido Aspártico/análogos & derivados , Creatina/metabolismo , Demência/metabolismo , Lobo Frontal/metabolismo , Degeneração Lobar Frontotemporal/metabolismo , Inositol/metabolismo , Proteínas tau/metabolismo , Adulto , Ácido Aspártico/metabolismo , Doenças Assintomáticas , Biomarcadores/metabolismo , Estudos de Casos e Controles , Demência/complicações , Demência/genética , Feminino , Degeneração Lobar Frontotemporal/complicações , Degeneração Lobar Frontotemporal/diagnóstico , Heterozigoto , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Espectroscopia de Prótons por Ressonância Magnética , Adulto Jovem , Proteínas tau/genética
10.
Braz J Med Biol Res ; 52(6): e8589, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31166385

RESUMO

The transport of myo-inositol is the main mechanism for the maintenance of its high intracellular levels. We aimed to measure the mRNA and protein levels of myo-inositol cotransporters in the sciatic nerve (SN) and dorsal root ganglia (DRG) during experimental diabetes. Streptozotocin-induced (STZ; 4, 8, and 12 weeks; 65 mg/kg; ip) diabetic rats (DB) and age-matched euglycemic (E) rats were used for the analysis of mRNA and protein levels of sodium myo-inositol cotransporters 1, 2 (SMIT1, SMIT2) or H+/myo-inositol cotransporter (HMIT). There was a significant reduction in the mRNA levels for SMIT1 in the SN and DRG (by 36.9 and 31.0%) in the 4-week DB (DB4) group compared to the E group. SMIT2 was not expressed in SN. The mRNA level for SMIT2 was up-regulated only in the DRG in the DB4 group. On the other hand, the protein level of SMIT1 decreased by 42.5, 41.3, and 44.8% in the SN after 4, 8, and 12 weeks of diabetes, respectively. In addition, there was a decrease of 64.3 and 58.0% of HMIT in membrane and cytosolic fractions, respectively, in the SN of the DB4 group. In the DRG, there was an increase of 230 and 86.3% for SMIT1 and HMIT, respectively, in the DB12 group. The levels of the main inositol transporters, SMIT1 and HMIT, were greatly reduced in the SN but not in the DRG. SMIT-1 was selectively reduced in the sciatic nerve during experimental STZ-induced diabetes.


Assuntos
Transporte Biológico Ativo/fisiologia , Diabetes Mellitus Experimental/metabolismo , Gânglios Espinais/metabolismo , Inositol/metabolismo , RNA Mensageiro/metabolismo , Nervo Isquiático/metabolismo , Animais , Western Blotting , Masculino , Ratos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Estreptozocina , Regulação para Cima
11.
Tuberculosis (Edinb) ; 116: 44-55, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31153518

RESUMO

Low molecular weight (LMW) thiols are molecules with a functional sulfhydryl group that enable them to detoxify reactive oxygen species, reactive nitrogen species and other free radicals. Their roles range from their ability to modulate the immune system to their ability to prevent damage of biological molecules such as DNA and proteins by protecting against oxidative, nitrosative and acidic stress. LMW thiols are synthesized and found in both eukaryotes and prokaryotes. Due to their beneficial role to both eukaryotes and prokaryotes, their specific functions need to be elucidated, most especially in pathogenic prokaryotes such as Mycobacterium tuberculosis (M.tb), in order to provide a rationale for targeting their biosynthesis for drug development. Ergothioneine (ERG), mycothiol (MSH) and gamma-glutamylcysteine (GGC) are LMW thiols that have been shown to interplay to protect M.tb against cellular stress. Though ERG, MSH and GGC seem to have overlapping functions, studies are gradually revealing their unique physiological roles. Understanding their unique physiological role during the course of tuberculosis (TB) infection, would pave the way for the development of drugs that target their biosynthetic pathway. This review identifies the knowledge gap in the unique physiological roles of LMW thiols and proposes their mechanistic roles based on previous studies. In addition, it gives an update on identified inhibitors of their biosynthetic enzymes.


Assuntos
Mycobacterium tuberculosis/metabolismo , Compostos de Sulfidrila/metabolismo , Tuberculose/microbiologia , Animais , Antituberculosos/uso terapêutico , Cisteína/metabolismo , Dipeptídeos/metabolismo , Inibidores Enzimáticos/uso terapêutico , Enzimas/metabolismo , Ergotioneína/metabolismo , Glicopeptídeos/metabolismo , Humanos , Inositol/metabolismo , Terapia de Alvo Molecular , Peso Molecular , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/patogenicidade , Tuberculose/tratamento farmacológico
12.
Eur J Radiol ; 116: 55-60, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31153574

RESUMO

OBJECTIVE: To determine the changes in fractional anisotropy (FA) at the proximal spinal cord and in magnetic resonance spectroscopy (MRS) of the precentral gyrus in patients with cervical spondylotic myelopathy (CSM) with respect to clinical symptoms and their duration. MATERIAL AND METHODS: 20 patients with CSM (7 female; mean age 64.6 ± 10.5 years) and 18 age/sex matched healthy controls (9 female; mean age 63.5 ± 6.6 years) were prospectively included. Clinical data (modified Japanese Orthopaedic Association Score (mJOA) and Neck Disability Index (NDI)) and 3T MR measurements including DTI at the spinal cord (level C2/3) with FA and MRS of the left and right precentral gyrus were taken. Clinical correlations and regression analyses were performed. RESULTS: Mean clinical scores of patients were significantly different to controls (mJOA; CSM: 10.2 ± 2.9; controls: 18.0 ± 0.0, p < 0.001; NDI; CSM: 41.4±23.5; controls: 4.4±6.6, p<0.001); FA was significantly lower in patients (CSM: 0.645 ± 0.067; controls: 0.699 ± 0.037, p = 0.005). MRS showed significantly lower metabolite concentrations between both groups: creatine (Cr) (CSM: 46.46±7.64; controls: 51.36±5.76, p = 0.03) and N-acetylaspartate (NAA) (CSM: 93.94±19.22; controls: 107.24±20.20, p = 0.05). Duration of symptoms ≤6 months was associated with increased myo-inositol (Ins) (61.58±17.76; 44.44±10.79; p = 0.02) and Ins/Cr ratio (1.36±0.47; 0.96±0.18; p = 0.014) compared to symptoms >6 months. CONCLUSION: Metabolic profiles of the precentral gyrus and FA in the uppermost spinal cord differ significantly between patients and healthy controls. Ins, thought to be a marker of endogenous neuroinflammatory response, is high in the early course of CSM and normalizes over time.


Assuntos
Espectroscopia de Ressonância Magnética/métodos , Córtex Motor/diagnóstico por imagem , Córtex Motor/metabolismo , Doenças da Medula Espinal/patologia , Espondilose/patologia , Idoso , Anisotropia , Ácido Aspártico/análogos & derivados , Ácido Aspártico/metabolismo , Biomarcadores/metabolismo , Vértebras Cervicais/diagnóstico por imagem , Vértebras Cervicais/patologia , Creatina/metabolismo , Feminino , Humanos , Inositol/metabolismo , Masculino , Pessoa de Meia-Idade , Córtex Motor/patologia , Doenças da Medula Espinal/metabolismo , Espondilose/metabolismo , Fatores de Tempo
13.
Enzyme Microb Technol ; 127: 70-74, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31088620

RESUMO

D-glucuronic acid (GlcUA) is an important intermediate with numerous applications in the food, cosmetics, and pharmaceutical industries. Its biological production routes which employ myo-inositol oxygenase (MIOX) as the key enzyme are attractive. In this study, five diverse MIOX-encoding genes, from Cryptococcus neoformans, Chaetomium thermophilum, Arabidopsis thaliana, Thermothelomyces thermophila, and Mus musculus were overexpressed in Escherichia coli, respectively. A novel MIOX from Thermothelomyces thermophila (TtMIOX) exhibited high specific activity, and efficiently converted myo-inositol to GlcUA. Meanwhile, the degradation of GlcUA was inhibited by inactivation of uxaC from the Escherichia coli genome. Finally, the BWΔuxaC whole-cell biocatalyst harboring TtMIOX resulted in the production of 106 g/L GlcUA within 12 h in a 1-L bioreactor, corresponding to a conversion of 91% and productivity of 8.83 g/L/h. This study provides a feasible method for the industrial production of GlcUA.


Assuntos
Escherichia coli/metabolismo , Expressão Gênica , Ácido Glucurônico/metabolismo , Inositol Oxigenase/metabolismo , Inositol/metabolismo , Proteínas Recombinantes/metabolismo , Sordariales/enzimologia , Animais , Arabidopsis/enzimologia , Arabidopsis/genética , Biotransformação , Chaetomium/enzimologia , Chaetomium/genética , Cryptococcus neoformans/enzimologia , Cryptococcus neoformans/genética , Escherichia coli/genética , Inositol Oxigenase/genética , Camundongos , Proteínas Recombinantes/genética , Sordariales/genética
14.
Neuroimage ; 191: 457-469, 2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-30818026

RESUMO

Reactive astrocytes exhibit hypertrophic morphology and altered metabolism. Deciphering astrocytic status would be of great importance to understand their role and dysregulation in pathologies, but most analytical methods remain highly invasive or destructive. The diffusion of brain metabolites, as non-invasively measured using diffusion-weighted magnetic resonance spectroscopy (DW-MRS) in vivo, depends on the structure of their micro-environment. Here we perform advanced DW-MRS in a mouse model of reactive astrocytes to determine how cellular compartments confining metabolite diffusion are changing. This reveals myo-inositol as a specific intra-astrocytic marker whose diffusion closely reflects astrocytic morphology, enabling non-invasive detection of astrocyte hypertrophy (subsequently confirmed by confocal microscopy ex vivo). Furthermore, we measure massive variations of lactate diffusion properties, suggesting that intracellular lactate is predominantly astrocytic under control conditions, but predominantly neuronal in case of astrocyte reactivity. This indicates massive remodeling of lactate metabolism, as lactate compartmentation is tightly linked to the astrocyte-to-neuron lactate shuttle mechanism.


Assuntos
Astrócitos/metabolismo , Encéfalo/metabolismo , Inositol/análise , Espectroscopia de Ressonância Magnética/métodos , Animais , Biomarcadores/análise , Biomarcadores/metabolismo , Imagem de Difusão por Ressonância Magnética , Inositol/metabolismo , Ácido Láctico/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL
15.
Nature ; 568(7750): 43-48, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30918406

RESUMO

Differences in the presence of even a few genes between otherwise identical bacterial strains may result in critical phenotypic differences. Here we systematically identify microbial genomic structural variants (SVs) and find them to be prevalent in the human gut microbiome across phyla and to replicate in different cohorts. SVs are enriched for CRISPR-associated and antibiotic-producing functions and depleted from housekeeping genes, suggesting that they have a role in microbial adaptation. We find multiple associations between SVs and host disease risk factors, many of which replicate in an independent cohort. Exploring genes that are clustered in the same SV, we uncover several possible mechanistic links between the microbiome and its host, including a region in Anaerostipes hadrus that encodes a composite inositol catabolism-butyrate biosynthesis pathway, the presence of which is associated with lower host metabolic disease risk. Overall, our results uncover a nascent layer of variability in the microbiome that is associated with microbial adaptation and host health.


Assuntos
Bactérias/genética , Suscetibilidade a Doenças/microbiologia , Microbioma Gastrointestinal/genética , Genes Bacterianos/genética , Variação Genética , Saúde , Interações entre Hospedeiro e Microrganismos/genética , Adaptação Fisiológica/genética , Bactérias/classificação , Bactérias/crescimento & desenvolvimento , Bactérias/metabolismo , Butiratos/metabolismo , Estudos de Coortes , Ecossistema , Eubacterium/genética , Eubacterium/metabolismo , Fezes/microbiologia , Microbioma Gastrointestinal/fisiologia , Interações entre Hospedeiro e Microrganismos/fisiologia , Humanos , Inositol/metabolismo , Metagenômica , Viabilidade Microbiana/genética , Fatores de Risco
16.
Poult Sci ; 98(9): 3870-3883, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-30877748

RESUMO

This study was conducted to evaluate the effect of microbial phytase and myo-inositol supplementation in low non-phytate phosphorus (nPP) diets on pH and the solubility of minerals in an in vitro digestion procedure (IVDP) and to compare this with digesta from birds fed different diets (grower diets) compared to the in vitro test (starter diets). A total of 660 1-day-old broilers were randomly allotted into 11 dietary treatments and fed a corn-soybean-meal-based diet with recommended nPP (positive control; PC), an nPP-deficient diet (negative control; NC), NC diets supplemented with phytase (500; 1,000; 2,000; 3,000; 4,000; 5,000; and 6,000 FTU/kg), an NC diet plus 0.15% myo-inositol, and an NC diet with reduced Ca level (Ca: nPP ratio same as PC) from 1 to 23 D of age. The pH and Ca solubility of the NC diet was increased compared with the PC when subjected to IVDP (P < 0.05). P solubility in the gizzard and jejunal digesta was reduced in the NC compared with the PC diet and this was also reflected in the IVDP. Phytase addition to the NC diets linearly increased (P < 0.05) the pH value and Ca and P solubilities in both digesta and diets subjected to IVDP. Higher doses of microbial phytase increased (P < 0.05) Zn and Fe solubilities in both digesta and IVDP. Myo-inositol supplementation of the NC diet had no effect on mineral solubility, but decreased (P < 0.05) the pH of the IVDP. Lowering the Ca content of the NC diet decreased (P < 0.05) the pH of the in vitro digested diets and Ca solubility in both broiler digesta and IVDP and also increased (P < 0.05) P solubility in both the jejunal digesta and IVDP. Correlations were noted between the solubility of P in the in vitro assay and that in the gizzard and jejunal digesta, and also with bird performance, confirms the usefulness of in vitro assay.


Assuntos
6-Fitase/metabolismo , Galinhas/fisiologia , Digestão/efeitos dos fármacos , Inositol/metabolismo , Minerais/metabolismo , Fósforo na Dieta/metabolismo , 6-Fitase/administração & dosagem , Ração Animal/análise , Animais , Galinhas/crescimento & desenvolvimento , Dieta/veterinária , Suplementos Nutricionais/análise , Relação Dose-Resposta a Droga , Concentração de Íons de Hidrogênio , Inositol/administração & dosagem , Distribuição Aleatória , Solubilidade
17.
Curr Genet ; 65(4): 995-1014, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30879088

RESUMO

In yeast, the GCR1 transcription factor is involved in the regulation of glycolysis and its deletion exhibited growth defect, reduced inositol and phosphatidylinositol (PI) levels compared to WT cells. We observed a down regulation of the INO1 and PIS1 expression in gcr1∆ cells under both I- and I+ conditions and the over expression of GCR1 in gcr1∆ cells restored the growth, retrieved the expression of INO1, and PIS1 comparable to WT cells. In the gel shift assay, the Gcr1p binds to its consensus sequence CTTCC in PIS1 promoter and regulates its expression but not in INO1 transcription. The WT cells, under I- significantly reduced the expression of GCR1 and PIS1, but increased the expression of KCS1 and de-repressed INO1. The Kcs1p expression was reduced in gcr1∆ cells; this reduced INO1 expression resulting in abnormal vacuolar structure and reduced autophagy in Saccharomyces cerevisiae.


Assuntos
Autofagia/genética , Proteínas de Ligação a DNA/genética , Proteínas de Saccharomyces cerevisiae/genética , Fatores de Transcrição/genética , Transcrição Genética , Sítios de Ligação , Proteínas de Ligação a DNA/química , Regulação Fúngica da Expressão Gênica/genética , Glicólise/genética , Inositol/genética , Inositol/metabolismo , Regiões Promotoras Genéticas , Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/química , Fatores de Transcrição/química , Vacúolos/genética , Vacúolos/ultraestrutura
18.
PLoS One ; 14(2): e0212002, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30789943

RESUMO

Neuroinflammation plays an important role in the pathogenesis of a range of brain disorders. Non-invasive imaging of neuroinflammation is critical to help improve our understanding of the underlying disease mechanisms, monitor therapies and guide drug development. Generally, MRI lacks specificity to molecular imaging biomarkers, but molecular MR imaging based on chemical exchange saturation transfer (CEST) can potentially detect changes of myoinositol, a putative glial marker that may index neuroinflammation. In this pilot study we aimed to investigate, through validation with immunohistochemistry and in vivo magnetic resonance spectroscopy (MRS), whether CEST imaging can reflect the microglial response to a mild inflammatory challenge with lipopolysaccharide (LPS), in the APPSwe/ PS1 mouse model of Alzheimer's disease and wild type controls. The response to the immune challenge was variable and did not align with genotype. Animals with a strong response to LPS (Iba1+, n = 6) showed an increase in CEST contrast compared with those who did not (Iba1-, n = 6). Changes of myoinositol levels after LPS were not significant. We discuss the difficulties of this mild inflammatory model, the role of myoinositol as a glial biomarker, and the technical challenges of CEST imaging at 0.6ppm.


Assuntos
Doença de Alzheimer/metabolismo , Proteínas de Ligação ao Cálcio/metabolismo , Inositol/metabolismo , Lipopolissacarídeos/efeitos adversos , Proteínas dos Microfilamentos/metabolismo , Animais , Modelos Animais de Doenças , Feminino , Interpretação de Imagem Assistida por Computador , Espectroscopia de Ressonância Magnética , Camundongos , Imagem Molecular , Neuroglia/metabolismo , Projetos Piloto , Regulação para Cima
19.
Methods Mol Biol ; 1949: 23-34, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30790246

RESUMO

There are several difficulties to face when investigating the role of phosphoinositides. Although they are present in most organelles, their concentration is very low, sometimes undetectable with the available methods; moreover, their level can quickly change upon several external stimuli. Here we introduce a newly improved lipid sensor tool-set based on the balanced expression of luciferase-fused phosphoinositide recognizing protein domains and a Venus protein targeted to the plasma membrane, allowing us to perform Bioluminescence Resonance Energy Transfer (BRET) measurements that reflect phosphoinositide changes in a population of transiently transfected cells. This method is highly sensitive, specific, and capable of semiquantitative characterization of plasma membrane phosphoinositide changes with high temporal resolution.


Assuntos
Técnicas de Transferência de Energia por Ressonância de Bioluminescência , Técnicas Biossensoriais , Membrana Celular/metabolismo , Inositol/metabolismo , Animais , Linhagem Celular , Análise de Dados , Humanos , Metabolismo dos Lipídeos
20.
Neurology ; 92(5): e395-e405, 2019 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-30610093

RESUMO

OBJECTIVE: To investigate the association between longitudinal changes in proton magnetic resonance spectroscopy (MRS) metabolites and amyloid pathology in individuals without dementia, and to explore the relationship between MRS and cognitive decline. METHODS: In this longitudinal multiple time point study (a subset of the Swedish BioFINDER), we included cognitively healthy participants, individuals with subjective cognitive decline, and individuals with mild cognitive impairment. MRS was acquired serially in 294 participants (670 individual spectra) from the posterior cingulate/precuneus. Using mixed-effects models, we assessed the association between MRS and baseline ß-amyloid (Aß), and between MRS and the longitudinal Mini-Mental State Examination, accounting for APOE, age, and sex. RESULTS: While baseline MRS metabolites were similar in Aß positive (Aß+) and negative (Aß-) individuals, in the Aß+ group, the estimated rate of change was +1.9%/y for myo-inositol (mI)/creatine (Cr) and -2.0%/y for N-acetylaspartate (NAA)/mI. In the Aß- group, mI/Cr and NAA/mI yearly change was -0.05% and +1.2%; however, this was not significant across time points. The mild cognitive impairment Aß+ group showed the steepest MRS changes, with an estimated rate of +2.93%/y (p = 0.07) for mI/Cr and -3.55%/y (p < 0.01) for NAA/mI. Furthermore, in the entire cohort, we found that Aß+ individuals with low baseline NAA/mI had a significantly higher rate of cognitive decline than Aß+ individuals with high baseline NAA/mI. CONCLUSION: We demonstrate that the longitudinal change in mI/Cr and NAA/mI is associated with underlying amyloid pathology. MRS may be a useful noninvasive marker of Aß-related processes over time. In addition, we show that in Aß+ individuals, baseline NAA/mI may predict the rate of future cognitive decline.


Assuntos
Peptídeos beta-Amiloides/metabolismo , Encéfalo/metabolismo , Inositol/metabolismo , Idoso , Ácido Aspártico/análogos & derivados , Ácido Aspártico/metabolismo , Biomarcadores/metabolismo , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/patologia , Creatina/metabolismo , Estudos Transversais , Programas de Triagem Diagnóstica , Progressão da Doença , Feminino , Humanos , Estudos Longitudinais , Masculino , Espectroscopia de Prótons por Ressonância Magnética
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