Ergothioneine Distribution in Bovine and Porcine Ocular Tissues

Shires, Thomas K.; Brummel, Marvin C.; Pulido, José S.; Stegink, Lewis D.

doi:10.1016/s0742-8413(96)00223-x

Cited by 42 publications

(36 citation statements)

References 10 publications

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“…In both C. graminicola and N. crassa conidia, EGT is present in a higher concentration than GSH. EGT is concentrated in certain animal tissues; in bovine eye lenses, EGT is in approximately 10-fold higher concentration than GSH (Shires et al, 1997). The localization of both NcEgt-1 and EGT is unknown; the homolog of NcEgt-1 in Schizosaccharomyces pombe (SPBC1604.01) apparently is present in both the nucleus and the cytoplasm (Matsuyama et al, 2006).…”

Section: Detection Quantification and Dynamics Of Ergothioneinementioning

confidence: 99%

“…The concentration of EGT in animal tissue is partly diet-dependent (Melville et al, 1955). However, animals have an EGT transporter, OCTN1 in humans (Gründemann et al, 2005), and EGT is concentrated from approximately 2-133 ng mg À1 fresh weight in specific tissues, especially in seminal fluid, erythrocytes, kidney, liver and eye cornea tissue (Melville et al, 1954;Shires et al, 1997). Although the role of EGT in animal tissue is unknown, the literature suggests that it may be involved as an antioxidant (Akanmu et al, 1991;Hartman, 1990) in seminal fluid (Mann et al, 1963), red blood cells (Melville et al, 1955), and in the following tissues: skin (Markova et al, 2009); kidney (Deiana et al, 2004), liver (Deiana et al, 2004), brain (Song et al, 2010), and eyes (Shires et al, 1997).…”

Section: Introductionmentioning

confidence: 99%

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The Neurospora crassa mutant NcΔEgt-1 identifies an ergothioneine biosynthetic gene and demonstrates that ergothioneine enhances conidial survival and protects against peroxide toxicity during conidial germination

Bello

Barrera-Perez

Morin

et al. 2012

Fungal Genetics and Biology

112

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Section: Detection Quantification and Dynamics Of Ergothioneinementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The Neurospora crassa mutant NcΔEgt-1 identifies an ergothioneine biosynthetic gene and demonstrates that ergothioneine enhances conidial survival and protects against peroxide toxicity during conidial germination

Bello

Barrera-Perez

Morin

et al. 2012

Fungal Genetics and Biology

112

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“…Higher organisms obtain EGT in food and accumulate it in certain tissues up to millimolar levels [2], [3] through a specific transporter, ETT/OCTN1 [4]. In mammals, large amounts of EGT are found in erythrocytes, bone marrow, liver, kidney, eye lens, and seminal fluid [2], [5], [6]. Nevertheless, EGT is neither a nutrient (it is virtually unmetabolized in humans) nor a vitamin (it is non-essential).…”

Section: Introductionmentioning

confidence: 99%

Genetic and Metabolomic Dissection of the Ergothioneine and Selenoneine Biosynthetic Pathway in the Fission Yeast, S. pombe, and Construction of an Overproduction System

2014

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Ergothioneine is a small, sulfur-containing metabolite (229 Da) synthesized by various species of bacteria and fungi, which can accumulate to millimolar levels in tissues or cells (e.g. erythrocytes) of higher eukaryotes. It is commonly marketed as a dietary supplement due to its proposed protective and antioxidative functions. In this study we report the genes forming the two-step ergothioneine biosynthetic pathway in the fission yeast, Schizosaccharomyces pombe. We identified the first gene, egt1+ (SPBC1604.01), by sequence homology to previously published genes from Neurospora crassa and Mycobacterium smegmatis. We showed, using metabolomic analysis, that the Δegt1 deletion mutant completely lacked ergothioneine and its precursors (trimethyl histidine/hercynine and hercynylcysteine sulfoxide). Since the second step of ergothioneine biosynthesis has not been characterized in eukaryotes, we examined four putative homologs (Nfs1/SPBC21D10.11c, SPAC11D3.10, SPCC777.03c, and SPBC660.12c) of the corresponding mycobacterial enzyme EgtE. Among deletion mutants of these genes, only one (ΔSPBC660.12c, designated Δegt2) showed a substantial decrease in ergothioneine, accompanied by accumulation of its immediate precursor, hercynylcysteine sulfoxide. Ergothioneine-deficient strains exhibited no phenotypic defects during vegetative growth or quiescence. To effectively study the role of ergothioneine, we constructed an egt1+ overexpression system by replacing its native promoter with the nmt1+ promoter, which is inducible in the absence of thiamine. We employed three versions of the nmt1 promoter with increasing strength of expression and confirmed corresponding accumulations of ergothioneine. We quantified the intracellular concentration of ergothioneine in S. pombe (0.3, 157.4, 41.6, and up to 1606.3 µM in vegetative, nitrogen-starved, glucose-starved, and egt1+-overexpressing cells, respectively) and described its gradual accumulation under long-term quiescence. Finally, we demonstrated that the ergothioneine pathway can also synthesize selenoneine, a selenium-containing derivative of ergothioneine, when the culture medium is supplemented with selenium. We further found that selenoneine biosynthesis involves a novel intermediate compound, hercynylselenocysteine.

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“…Although it is not made in the human body, some human tissues contain high concentrations of ergothioneine. Relatively high levels of ergothioneine are present in bovine and porcine ocular tissues, including aqueous humor, where it likely protects ocular tissues from oxidative damage (Shires et al, 1997). Carnitine is important for conversion of fatty acids into metabolic energy and acts as an antioxidant.…”

Section: Perspectivesmentioning

confidence: 99%

Drug Transport by the Blood-Aqueous Humor Barrier of the Eye

Lee

Pelis

2016

Drug Metabolism and Disposition

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The ocular barriers (cornea, blood-retinal barrier, and blood-aqueous humor barrier) make treating eye diseases with therapeutic drugs challenging. The tight capillary endothelium of the iris and the ciliary body epithelium form the blood-aqueous humor barrier. The iris and ciliary body (iris-ciliary body) express a variety of drug transporters in the ATP-binding cassette and solute carrier (SLC) families. ATPbinding cassette family drug transporters that are present in the irisciliary body include P-glycoprotein, breast cancer resistance protein, and several multidrug resistance-associated proteins. SLC family drug transporters that are present in the iris-ciliary body include organic anion transporters, organic anion transporting polypeptides, bile acid transporters (apical sodium-dependent bile salt transporter and sodium taurocholate cotransporter), organic cation transporters (novel organic cation transporter and multidrug and toxin extrusion transporter) and peptide transporters. Freshly dissected iris-ciliary body preparations actively accumulate a variety of substrates of SLC drug transporters that are expressed in the tissue. The ciliary body in vitro supports active transport in the aqueous humor-to-blood direction of several substrates of organic anion transporters and multidrug resistance-associated proteins, consistent with the subcellular localization of these transporters in the ciliary body epithelium. In vivo data suggest that drug transporters in the iris-ciliary body reduce the permeation of drugs in the direction of blood-toaqueous humor, thereby reducing ocular drug bioavailability, and are also involved in active drug elimination from the aqueous humor. An understanding of the influence on pharmacokinetics of drug transporters in the blood-aqueous humor barrier should help improve drug delivery and efficacy in the eye.

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Ergothioneine Distribution in Bovine and Porcine Ocular Tissues

Cited by 42 publications

References 10 publications

The Neurospora crassa mutant NcΔEgt-1 identifies an ergothioneine biosynthetic gene and demonstrates that ergothioneine enhances conidial survival and protects against peroxide toxicity during conidial germination

The Neurospora crassa mutant NcΔEgt-1 identifies an ergothioneine biosynthetic gene and demonstrates that ergothioneine enhances conidial survival and protects against peroxide toxicity during conidial germination

Genetic and Metabolomic Dissection of the Ergothioneine and Selenoneine Biosynthetic Pathway in the Fission Yeast, S. pombe, and Construction of an Overproduction System

Drug Transport by the Blood-Aqueous Humor Barrier of the Eye

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