Ergothioneine Modulates Proinflammatory Cytokines and Heat Shock Protein 70 in Mesenteric Ischemia and Reperfusion Injury

Şakrak, Ömer; Kerem, Mustafa; Bedirli, Abdülkadir; Paşaoğlu, Hatîce; Akyürek, Nalân; Ofluoglu, Ebru; Gültekin, Fatma Ayça

doi:10.1016/j.jss.2007.04.020

Cited by 62 publications

(42 citation statements)

References 32 publications

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“…Exogenous administration of ergothioneine was reported to ameliorate oxidative stress in various tissues, including small intestine (24). Therefore, the effect of ergothioneine treatment on clinical symptoms of CD patients needs to be examined to clarify whether ergothioneine has a potential ameliorating effect on the intestinal inflammation.…”

Section: Discussionmentioning

confidence: 99%

“…At such a concentration, ergothioneine behaves as a powerful chemical scavenger of a number of oxidizing species (23). In addition, ergothioneine was found to be highly accumulated in small intestine (Figure 4), and exogenous administration of ergothioneine was reported to ameliorate oxidative stress in various tissues, including small intestine (24). These data led us to examine whether or not octn1 -/-mice were more sensitive to small intestinal injury.…”

Section: Intestinal Absorption Distribution To Small Intestine and Rmentioning

confidence: 98%

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Gene Knockout and Metabolome Analysis of Carnitine/Organic Cation Transporter OCTN1

et al. 2010

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Purpose: Solute carrier, OCTN1 (SLC22A4) is an orphan transporter, the physiologically important substrate of which is still unidentified. The aim of the present study was to examine physiological roles of OCTN1. Methods:We first constructed octn1 gene knockout (octn1 -/-) mice. Metabolome analysis was then performed to identify substrates in vivo. The possible association of the substrate identified with diseased conditions was further examined. Results:The metabolome analysis of blood and several organs indicated complete deficiency of a naturally occurring potent antioxidant ergothioneine in octn1 -/-mice among 112 metabolites examined.Pharmacokinetic analyses after oral administration revealed the highest distribution to small intestines and extensive renal reabsorption of [ 3 H]ergothioneine, both of which were much reduced in octn1 -/-mice.The octn1 -/-mice exhibited greater susceptibility to intestinal inflammation under the ischemia and reperfusion model. The blood ergothioneine concentration was also much reduced in Japanese patients with Crohn's disease, compared with healthy volunteers and patients with another inflammatory bowel disease, ulcerative colitis. 4Conclusions: These results indicate that OCTN1 plays a pivotal role for maintenance of systemic and intestinal exposure of ergothioneine which could be important for protective effect against intestinal tissue injuries, providing a possible diagnostic tool to distinguish the inflammatory bowel diseases.

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Section: Discussionmentioning

confidence: 99%

Section: Intestinal Absorption Distribution To Small Intestine and Rmentioning

confidence: 98%

Gene Knockout and Metabolome Analysis of Carnitine/Organic Cation Transporter OCTN1

et al. 2010

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“…liver by increasing heat shock proteins-70 and decreasing tumor necrosis factor-a, interleukin-1b, malondialdehyde, and myeloperoxidase levels in the tissues (Bedirli et al, 2004;Sakrak et al, 2008). Ergothioneine is obtained from diet and its concentration in human blood ranges from 11.9 to 13.5 mg/l (i.e., 51.9 to 58.9 mM) for normal subjects, 11.6 to 13.6 mg/l (i.e., 50.6 to 60.1 mM) for type I diabetic subjects, and 11.9 to 21.9 (i.e., 51.9 to 95.5 mM) for type II diabetic subjects (Epand et al, 1988).…”

Section: Ergothioneine Protects Endothelial Cellsmentioning

confidence: 99%

“…Oral administration of ergothioneine protects fatty acids against ferric-nitrilotriacetate-induced oxidation in rat kidney and liver (Deiana et al, 2004). In vivo treatment of rats with ergothioneine also protects intestinal and liver tissues from damage during ischemia/reperfusion injury (Bedirli et al, 2004;Sakrak et al, 2008). In addition, chronic administration of ergothioneine inhibits brain lipid peroxidation, protects against cisplatin-induced neuronal injury, and enhances cognition in the mouse (Song et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

Uptake and Protective Effects of Ergothioneine in Human Endothelial Cells

Yang²,

Sit

et al. 2014

The Journal of Pharmacology and Experimental Therapeutics

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Ergothioneine is a thiourea derivative of histidine found in food, especially mushrooms. Experiments in cell-free systems and chemical assays identified this compound as a powerful antioxidant. Experiments were designed to test the ability of endothelial cells to take up ergothioneine and hence benefit from protection against oxidative stress. Reverse-transcription polymerase chain reaction and Western blotting demonstrated transcription and translation of an ergothioneine transporter in human brain microvascular endothelial cells (HBMECs). Uptake of [3 H]ergothioneine occurred by the organic cation transporter novel type-1 (OCTN-1), was sodium-dependent, and was reduced when expression of OCTN-1 was silenced by small interfering RNA (siRNA). The effect of ergothioneine on the production of reactive oxygen species (ROS) in HBMECs was measured using dichlorodihydrofluorescein and lucigenin, and the effect on cell viability was studied using the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay. ROS production and cell death induced by pyrogallol, xanthine oxidase plus xanthine, and high glucose were suppressed by ergothioneine. The antioxidant and cytoprotective effects of ergothioneine were abolished when OCTN-1 was silenced using siRNA. The expression of NADPH oxidase 1 was decreased, and those of glutathione reductase, catalase, and superoxide dismutase enhanced by the compound. In isolated rat basilar arteries, ergothioneine attenuated the reduction in acetylcholine-induced relaxation caused by pyrogallol, xanthine oxidase plus xanthine, or incubation in high glucose. Chronic treatment with the compound improved the response to acetylcholine in arteries of rats with streptozotocin-induced diabetes. In summary, ergothioneine is taken up by endothelial cells via OCTN-1, where the compound then protects against oxidative stress, curtailing endothelial dysfunction.

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“…SLC22A4 encodes carnitine/organic cation transporter (OCTN1), which transports ergothioneine. Ergothioneine was shown to have antioxidative and cytoprotective functions (37,38) and to protect cardiovascular tissue against oxidative injury during ischemia and reperfusion (39). Ergothioneine decreased the expression of the adhesion molecules, including vascular cell adhesion molecule 1, intercellular adhesion molecule 1 and selectin E, and inhibited binding of monocytes to the endothelium (40).…”

Section: Recessive Additive 1 Additive 2 ----------------------------mentioning

confidence: 99%

Association of TOMM40 and SLC22A4 polymorphisms with ischemic stroke

et al. 2015

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Abstract. Recent genome-wide association studies (GWASs) and their meta-analyses have identified various genes and loci underlying the predisposition to ischemic stroke or coronary artery disease in Caucasian populations. Given that ischemic stroke and coronary artery disease may have a shared genetic architecture, certain polymorphisms may confer genetic susceptibility to these two diseases. The aim of the present study was to examine the possible association of ischemic stroke with 29 single-nucleotide polymorphisms (SNPs) previously identified by the meta-analyses of GWASs as susceptibility loci for coronary artery disease. The study population comprised 3,187 Japanese individuals, including 894 subjects with ischemic stroke and 2,293 controls. The genotypes for the 29 SNPs of the 28 genes were determined by a method that combines the polymerase chain reaction and sequence-specific oligonucleotide probes with suspension array technology. Comparisons of the allele frequencies by the χ 2 test between subjects with ischemic stroke and controls revealed that rs9319428 (G→A) of the fms-related tyrosine kinase 1 gene (P=0.0471), rs2075650 (G→A) of the translocase of outer mitochondrial membrane 40 homolog gene (TOMM40, P=0.0102) and rs273909 (T→C) of the solute carrier family 22, member 4 gene (SLC22A4, P=0.0097) were significantly (P<0.05) associated with the prevalence of ischemic stroke. Multivariable logistic regression analysis with adjustment for age, gender, body mass index, smoking status and the prevalence of hypertension, diabetes mellitus and dyslipidemia revealed that rs2075650 of TOMM40 (P=0.0443; recessive model; odds ratio=0.50) and rs273909 of SLC22A4 (P= 0.0123; dominant model; odds ratio= 0.45) were significantly associated with ischemic stroke with the minor G and C allele, respectively, being protective against this condition. TOMM40 and SLC22A4 may thus be susceptibility loci for ischemic stroke in Japanese individuals.

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Ergothioneine Modulates Proinflammatory Cytokines and Heat Shock Protein 70 in Mesenteric Ischemia and Reperfusion Injury

Cited by 62 publications

References 32 publications

Gene Knockout and Metabolome Analysis of Carnitine/Organic Cation Transporter OCTN1

Gene Knockout and Metabolome Analysis of Carnitine/Organic Cation Transporter OCTN1

Uptake and Protective Effects of Ergothioneine in Human Endothelial Cells

Association of TOMM40 and SLC22A4 polymorphisms with ischemic stroke

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