scholarly journals The biology of ergothioneine, an antioxidant nutraceutical

2020 ◽  
Vol 33 (2) ◽  
pp. 190-217 ◽  
Author(s):  
Irina Borodina ◽  
Louise C. Kenny ◽  
Cathal M. McCarthy ◽  
Kalaivani Paramasivan ◽  
Etheresia Pretorius ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Amino Acid ◽  
Antioxidant Activities ◽  
Inflammatory Diseases ◽  
Regulatory Agencies ◽  
Fruiting Bodies ◽  
Solute Carrier Family ◽  
Chronic Inflammatory Diseases ◽  
The Status ◽  
Solute Carrier

AbstractErgothioneine (ERG) is an unusual thio-histidine betaine amino acid that has potent antioxidant activities. It is synthesised by a variety of microbes, especially fungi (including in mushroom fruiting bodies) and actinobacteria, but is not synthesised by plants and animals who acquire it via the soil and their diet, respectively. Animals have evolved a highly selective transporter for it, known as solute carrier family 22, member 4 (SLC22A4) in humans, signifying its importance, and ERG may even have the status of a vitamin. ERG accumulates differentially in various tissues, according to their expression of SLC22A4, favouring those such as erythrocytes that may be subject to oxidative stress. Mushroom or ERG consumption seems to provide significant prevention against oxidative stress in a large variety of systems. ERG seems to have strong cytoprotective status, and its concentration is lowered in a number of chronic inflammatory diseases. It has been passed as safe by regulatory agencies, and may have value as a nutraceutical and antioxidant more generally.

Exploiting Anti-Inflammation Effects of Flavonoids in Chronic Inflammatory Diseases

2020 ◽  
Vol 26 (22) ◽  
pp. 2610-2619 ◽  
Author(s):  
Tarique Hussain ◽  
Ghulam Murtaza ◽  
Huansheng Yang ◽  
Muhammad S. Kalhoro ◽  
Dildar H. Kalhoro
Keyword(s):  
Oxidative Stress ◽  
Chronic Diseases ◽  
Inflammatory Diseases ◽  
Therapeutic Option ◽  
Cellular Level ◽  
Antiinflammatory Drugs ◽  
Suitable Alternative ◽  
Chronic Inflammatory Diseases

Background: Inflammation is a complex response of the host defense system to different internal and external stimuli. It is believed that persistent inflammation may lead to chronic inflammatory diseases such as, inflammatory bowel disease, neurological and cardiovascular diseases. Oxidative stress is the main factor responsible for the augmentation of inflammation via various molecular pathways. Therefore, alleviating oxidative stress is effective a therapeutic option against chronic inflammatory diseases. Methods: This review article extends the knowledge of the regulatory mechanisms of flavonoids targeting inflammatory pathways in chronic diseases, which would be the best approach for the development of suitable therapeutic agents against chronic diseases. Results: Since the inflammatory response is initiated by numerous signaling molecules like NF-κB, MAPK, and Arachidonic acid pathways, their encountering function can be evaluated with the activation of Nrf2 pathway, a promising approach to inhibit/prevent chronic inflammatory diseases by flavonoids. Over the last few decades, flavonoids drew much attention as a potent alternative therapeutic agent. Recent clinical evidence has shown significant impacts of flavonoids on chronic diseases in different in-vivo and in-vitro models. Conclusion: Flavonoid compounds can interact with chronic inflammatory diseases at the cellular level and modulate the response of protein pathways. A promising approach is needed to overlook suitable alternative compounds providing more therapeutic efficacy and exerting fewer side effects than commercially available antiinflammatory drugs.

Amino acid transporter expression in the endometrium and conceptus membranes during early equine pregnancy

2018 ◽  
Vol 30 (12) ◽  
pp. 1675 ◽  
Author(s):  
Charlotte Gibson ◽  
Marta de Ruijter-Villani ◽  
Jolanda Rietveld ◽  
Tom A. E. Stout
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Early Pregnancy ◽  
Normal Pregnancy ◽  
Spatiotemporal Patterns ◽  
Solute Carrier Family ◽  
Conceptus Development ◽  
Solute Carrier ◽  
Adequate Nutrient ◽  
Transporter Expression

Maternally derived amino acids (AA) are essential for early conceptus development, and specific transporters enhance histotrophic AA content during early ruminant pregnancy. In the present study we investigated AA transporter expression in early equine conceptuses and endometrium, during normal pregnancy and after induction of embryo–uterus asynchrony. ‘Normal’ conceptuses and endometrium were recovered on Days 7, 14, 21 and 28 after ovulation. To investigate asynchrony, Day 8 embryos were transferred to recipient mares on Day 8 or Day 3, and conceptuses were recovered 6 or 11 days later. Endometrial expression of AA transporters solute carrier family 38 member 2 (SLC38A2), solute carrier family 1 members 4 and 5 (SLC1A4 and SLC1A5) increased during early pregnancy, whereas solute carrier family 7 member 8 (SLC7A8), solute carrier family 43 member 2 (SLC43A2) and solute carrier family 7 member 1 (SLC7A1) SLC7A8, SLC43A2 and SLC7A1 expression decreased and the expression of solute carrier family 1 member 1(SLC1A1) and solute carrier family 7 member 2 (SLC7A2) was unaffected. In conceptus membranes, most transporters studied were upregulated, either after Day 14 (solute carrier family 7 member 5 – SLC7A5, SLC38A2, SLC1A4, SLC1A5 and SLC7A1) or Day 21 (SLC43A2 and SLC7A2). Asynchronous ET indicated that endometrial SLC1A5, SLC1A1 and SLC7A8 are primarily regulated by conceptus factors and/or longer exposure to progesterone. In conclusion, AA transporters are expressed in early equine conceptus membranes and endometrium in specific spatiotemporal patterns. Because conceptuses express a wider range of transporters than the endometrium, we speculate that the equine yolk sac has recruited AA transporters to ensure adequate nutrient provision during an unusually long preimplantation period.

scholarly journals Molecular analysis of solute carrier family 11 member a1 (Slc11a1) gene in ruminants and non-ruminants using computational method

Genetika ◽  
2014 ◽  
Vol 46 (3) ◽  
pp. 925-934 ◽  
Author(s):  
Abdulmojeed Yakubu ◽  
Daniels Alade ◽  
Ndubuisi Dim
Keyword(s):  
Amino Acid ◽  
Metal Ion ◽  
Phylogenetic Trees ◽  
Computational Method ◽  
Natural Resistance ◽  
Solute Carrier Family ◽  
Synonymous Mutations ◽  
Slc11a1 Gene ◽  
Cellular Expression ◽  
Solute Carrier

Solute carrier family 11 member a1 gene (Slc11a1) previously known as natural resistance-associated macrophage protein 1 (Nramp1) is a gene of member of family of metal ion-transport protein. The cellular expression is restricted to phagocytic cells. Slc11a1 delivers bivalent metal cations from the cytosol into acidic endosomal and lysosomal compartments where Fenon and Haber-Weiss reaction generates toxic antimicrobial radicals for direct antimicrobial activity against harmful microorganisms. The present study was undertaken with the objective of analyzing Slc11a1 gene to gain insight into the evolutionary proximity and divergence as well as the polymorphism of this gene in ruminants and non-ruminants including the attendant effects of the genetic variants on the function of the Slc11a1 protein. Thirty Slc11a1 gene sequences of 6 mammalian species classified as ruminant (goat, sheep, cattle, Bubalus bubalis and Bubalus carabanensis) and non-ruminant (swine and horse) animals were investigated. The length of the Slc11a1 gene varied from 448-2,357. There was substantial genetic variation and polymorphism in the aligned sequences of Slc11a1 gene within and across species. Functional analysis of non-synonymous mutations in cattle revealed that twenty five of the amino acid substitutions at the peptide binding region could be beneficial, (E36G), (T52A), (N161S) and (V248I) were likely to be beneficial while only (Q312K) was harmful. In horse, two of the amino acid mutations were harmful, two were likely to be harmful, one was undecided, four were likely beneficial and the rest twenty were beneficial. The phylogenetic trees showed some form of proximity and differentiation in Slc11a1 sequences within and across species. The present information on the polymorphism of Slc11a1 gene might be exploited in the search for association with disease resistance in Nigerian livestock species.

scholarly journals Microarray analysis reveals the inhibition of intestinal expression of nutrient transporters in piglets infected with porcine epidemic diarrhea virus

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Junmei Zhang ◽  
Di Zhao ◽  
Dan Yi ◽  
Mengjun Wu ◽  
Hongbo Chen ◽  
...  
Keyword(s):  
Amino Acid ◽  
Amino Acid Transporter ◽  
Nutrient Transporters ◽  
Solute Carrier Family ◽  
Diarrhea Virus ◽  
Expression Of Genes ◽  
Sodium Dependent ◽  
Solute Carrier ◽  
Porcine Epidemic Diarrhea ◽  
Acid Transporter

AbstractPorcine epidemic diarrhea virus (PEDV) infection can induce intestinal dysfunction, resulting in severe diarrhea and even death, but the mode of action underlying these viral effects remains unclear. This study determined the effects of PEDV infection on intestinal absorption and the expression of genes for nutrient transporters via biochemical tests and microarray analysis. Sixteen 7-day-old healthy piglets fed a milk replacer were randomly allocated to one of two groups. After 5-day adaption, piglets (n = 8/group) were orally administrated with either sterile saline or PEDV (the strain from Yunnan province) at 104.5 TCID50 (50% tissue culture infectious dose) per pig. All pigs were orally infused D-xylose (0.1 g/kg BW) on day 5 post PEDV or saline administration. One hour later, jugular vein blood samples as well as intestinal samples were collected for further analysis. In comparison with the control group, PEDV infection increased diarrhea incidence, blood diamine oxidase activity, and iFABP level, while reducing growth and plasma D-xylose concentration in piglets. Moreover, PEDV infection altered plasma and jejunal amino acid profiles, and decreased the expression of aquaporins and amino acid transporters (L-type amino acid transporter 1, sodium-independent amino acid transporter, B(°,+)-type amino acid transport protein, sodium-dependent neutral amino acid transporter 1, sodium-dependent glutamate/aspartate transporter 3, and peptide transporter (1), lipid transport and metabolism-related genes (lipoprotein lipase, apolipoprotein A1, apolipoprotein A4, apolipoprotein C2, solute carrier family 27 member 2, solute carrier family 27 member 4, fatty acid synthase, and long-chain acyl-CoA synthetase (3), and glucose transport genes (glucose transporter-2 and insulin receptor) in the jejunum. However, PEDV administration increased mRNA levels for phosphoenolpyruvate carboxykinase 1, argininosuccinate synthase 1, sodium/glucose co-transporter-1, and cystic fibrosis transmembrane conductance regulator in the jejunum. Collectively, these comprehensive results indicate that PEDV infection induces intestinal injury and inhibits the expression of genes encoding for nutrient transporters.

scholarly journals Ozone in Medicine. The Low-Dose Ozone Concept and Its Basic Biochemical Mechanisms of Action in Chronic Inflammatory Diseases

2021 ◽  
Vol 22 (15) ◽  
pp. 7890
Author(s):  
Renate Viebahn-Haensler ◽  
Olga Sonia León Fernández
Keyword(s):  
Oxidative Stress ◽  
Clinical Trials ◽  
Low Dose ◽  
Inflammatory Diseases ◽  
Clinical Status ◽  
Limiting Factor ◽  
Chronic Inflammatory Diseases ◽  
Systemic Treatments ◽  
Medical Ozone ◽  
Set Up

Low-dose ozone acts as a bioregulator in chronic inflammatory diseases, biochemically characterized by high oxidative stress and a blocked regulation. During systemic applications, “Ozone peroxides” are able to replace H2O2 in its specific function of regulation, restore redox signaling, and improve the antioxidant capacity. Two different mechanisms have to be understood. Firstly, there is the direct mechanism, used in topical treatments, mostly via radical reactions. In systemic treatments, the indirect, ionic mechanism is to be discussed: “ozone peroxide” will be directly reduced by the glutathione system, informing the nuclear factors to start the regulation. The GSH/GSSG balance outlines the ozone dose and concentration limiting factor. Antioxidants are regulated, and in the case of inflammatory diseases up-regulated; cytokines are modulated, here downregulated. Rheumatoid arthritis RA as a model for chronic inflammation: RA, in preclinical and clinical trials, reflects the pharmacology of ozone in a typical manner: SOD (superoxide dismutase), CAT (catalase) and finally GSH (reduced glutathione) increase, followed by a significant reduction of oxidative stress. Inflammatory cytokines are downregulated. Accordingly, the clinical status improves. The pharmacological background investigated in a remarkable number of cell experiments, preclinical and clinical trials is well documented and published in internationally peer reviewed journals. This should encourage clinicians to set up clinical trials with chronic inflammatory diseases integrating medical ozone as a complement.

scholarly journals Lysosomal amino acid transporters as key players in inflammatory diseases

2021 ◽  
Author(s):  
Noriko Toyama-Sorimachi ◽  
Toshihiko Kobayashi
Keyword(s):  
Signal Transduction ◽  
Amino Acid ◽  
Immune Cells ◽  
Inflammatory Responses ◽  
Inflammatory Diseases ◽  
Metabolic Adaptation ◽  
Amino Acid Transporters ◽  
Proof Of Concept ◽  
Immune Mediated ◽  
Solute Carrier

Abstract Controlling inflammation can alleviate immune-mediated, lifestyle-related and neurodegenerative diseases. The endolysosome system plays critical roles in inflammatory responses. Endolysosomes function as signal transduction hubs to convert various environmental danger signals into gene expression, enabling metabolic adaptation of immune cells and efficient orchestration of inflammation. Solute carrier family 15 member 3 (SLC15A3) and member 4 (SLC15A4) are endolysosome-resident amino acid transporters that are preferentially expressed in immune cells. These transporters play essential roles in signal transduction through endolysosomes, and the loss of either transporter can alleviate multiple inflammatory diseases because of perturbed endolysosome-dependent signaling events, including inflammatory and metabolic signaling. Here, we summarize the findings leading to a proof-of-concept for anti-inflammatory strategies based on targeting SLC15 transporters.

Chronic Immune Stimulation May Cause Moderate Impairment of Phenylalanine 4-hydroxylase

Pteridines ◽  
2011 ◽  
Vol 22 (1) ◽  
pp. 120-125 ◽  
Author(s):  
S Scholl-Bürgi ◽  
S Schroecksnadel ◽  
M Jenny ◽  
D Karall ◽  
D Fuchs
Keyword(s):  
Amino Acid ◽  
Immune Activation ◽  
Clinical Relevance ◽  
Inflammatory Diseases ◽  
Immune Stimulation ◽  
Elevated Plasma ◽  
Chronic Inflammatory Diseases ◽  
Patients With Cancer ◽  
Classical Phenylketonuria ◽  
Hiv 1

Abstract Phenylalanine (4)-hydroxylase (PAH, E.C. 1.14.16.1) is located mainly in liver and converts amino acid phenylalanine (Phe) to tyrosine (Tyr). In 'classical' phenylketonuria (PKU), PAH activity is reduced, whereas in 'atypical' PKU biosynthesis of the cofactor 5,6,7,8-tetrahydrobiopterin (BH4) is disturbed. Aside from these inherited conditions, elevated plasma Phe concentrations and increased Phe to Tyr ratios (Phe/Tyr) were observed in patients with cancer, burns, sepsis and HIV-1 infection. Results indicate that immune activation and inflammation are associated with moderate impairment of PAH activity. This review discusses findings of increased Phe/Tyr in patients suffering from chronic inflammatory diseases, their clinical relevance and consequences.

scholarly journals SLC6 neurotransmitter transporter family (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database

2019 ◽  
Vol 2019 (4) ◽  
Author(s):  
Stefan Bröer ◽  
Gary Rudnick
Keyword(s):  
Amino Acids ◽  
Plasma Membrane ◽  
Amino Acid ◽  
Crystal Structures ◽  
Structural Motif ◽  
Solute Carrier Family ◽  
Neurotransmitter Transporter ◽  
Transporter Family ◽  
Bacterial Homolog ◽  
Solute Carrier

Members of the solute carrier family 6 (SLC6) of sodium- and (sometimes chloride-) dependent neurotransmitter transporters [29, 22, 70] are primarily plasma membrane located and may be divided into four subfamilies that transport monoamines, GABA, glycine and neutral amino acids, plus the related bacterial NSS transporters [99]. The members of this superfamily share a structural motif of 10 TM segments that has been observed in crystal structures of the NSS bacterial homolog LeuTAa, a Na+-dependent amino acid transporter from Aquiflex aeolicus [126] and in several other transporter families structurally related to LeuT [45].

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