-Gliotoxincontaining-organic-extracts-derived-from-A-a

fumigatus ATCC 26933 significantly inhibited (P < 05) the growth of the ΔgliK(26933) deletion mutant. The A. fumigatus ΔgliK(26933) mutant secreted metabolites, devoid of disulfide linkages or free thiols, that were detectable by reverse-phase high-performance liquid chromatography and liquid chromatography-mass spectrometry with m/z 394 to 396. These metabolites (m/z 394 to 396) were present at significantly higher levels in the culture supernatants of the A. fumigatus ΔgliK(26933) mutant than in those of the wild type (P = 0024 [fold difference, 24] and P = 0003 [fold difference, 9], respectively) and were absent from A. fumigatus ΔgliG.

Significantly elevated levels of ergothioneine were present in aqueous mycelial extracts of the A. fumigatus ΔgliK(26933) mutant compared to the wild type (P < 001). Determination of the gliotoxin uptake rate revealed a significant difference (P = 0045) between that of A. fumigatus ATCC 46645 (9 pg/mg mycelium/min) and the ΔgliK(46645) mutant (31 pg/mg mycelium/min), strongly suggesting that gliK absence and the presence of elevated ergothioneine levels impede exogenously added gliotoxin efflux. Our results confirm a role for gliK in gliotoxin biosynthesis and reveal new insights into gliotoxin functionality Association of rheumatoid arthritis with ergothioneine levels in red blood OBJECTIVE: The dietary thiol compound and erythrocyte ingredient ergothioneine (ET) is the preferential physiological substrate of the organic cation transporter OCTN1, found to be associated with rheumatoid arthritis (RA) in genetic studies, but the biological roles of ET and OCTN1 are unclear. We investigated the association between ET concentrations in peripheral blood erythrocytes and the occurrence of RA.METHODS: Erythrocyte ET concentrations in patients with mildly active RA (n = 73) were compared to ET levels in patients with coronary heart disease (CHD; n = 62) and osteoarthritis (OA; n = 148), serving as non-RA chronic inflammatory disease controls.

Correlation of ET levels in erythrocytes with levels of ET and OCTN1 mRNA in CD14+ monocytes was determined in 10 healthy subjects.RESULTS: Erythrocyte ET levels were significantly higher in patients with RA, with a median (interquartile range) of 12 micromole/l of erythrocytes (IQR 8-18), compared to 7 (IQR 5-12; p < 001) in CHD and 7 (IQR 4-12; p < 001) in OA. The prevalence of RA compared to non-RA controls increased with increasing blood ET concentrations, with an odds ratio of 03 (95% CI 03-01; p < 001) in the lowest quartile of RA erythrocyte ET levels to 31 (95% CI 14-69; p = 002) in the highest quartile. the ordinary cleanser in ET values were maintained after adjustment for disease-related anthropometric and clinical variables (age, sex, body mass index, smoking, duration of disease, hemoglobin, C-reactive protein, and medication) and were also independent of erythrocyte glutathione levels and of polymorphisms of the OCTN1 gene. ET levels in erythrocytes were linearly correlated with ET concentrations (R2 = 036, p < 001) and OCTN1 mRNA levels (R2 = 046, p < CONCLUSION: Mildly active cases of RA are associated with an unexplained high Ergothioneine rescues PC12 cells from beta-amyloid-induced apoptotic death.Seoul National University, Seoul 151-742, South Korea.Beta-amyloid (Abeta) peptide is the major component of senile plaques and considered to have a causal role in the development and progression of Alzheimer's disease.

There has been compelling evidence that Abeta-induced cytotoxicity is mediated through oxidative and/or nitrosative stress. Recently, considerable attention has been focused on dietary manipulation of oxidative and/or nitrosative damage. l-Ergothioneine (EGT; 2-mercaptohistidine trimethylbetaine) is a low-molecular-weight naturally occurring thiol compound of dietary origin that exists in the brain, liver, kidney, erythrocytes, ocular tissues, and seminal fluids of mammals. This water-soluble antioxidant has the ability to scavenge hydroxyl and peroxynitrite radicals as well as activated oxygen species, such as singlet oxygen. In this study, we investigated the effects of EGT on Abeta-induced oxidative and/or nitrosative cell death. Rat pheochromocytoma (PC12) cells treated with Abeta underwent apoptotic death as determined by positive in situ terminal end-labeling (TUNEL staining), decreased mitochondrial transmembrane potential, increased ratio of proapoptotic Bax to antiapoptotic Bcl-XL, elevated caspase-3 activity, and cleavage of poly(ADP-ribose) polymerase. squalane oil attenuated Abeta-induced apoptosis in PC12 cells.

Compared to N-acetyl-l-cysteine, which mainly scavenges reactive oxygen species, EGT effectively inhibited Abeta-induced cell death by suppressing peroxynitrite formation and subsequent nitration of protein tyrosine residues. The effects of EGT on the cytotoxicity induced by the nitric oxide donor sodium nitroprusside (SNP) and the peroxynitrite-generating 3-morpholinosydnonimine chlorhydrate (SIN-1) were compared. Whereas EGT significantly protected against SIN-1-mediated cell death, it barely affected the cytotoxicity induced by SNP. Thus EGT may attenuate apoptosis caused by Abeta, preferentially by eliminating peroxynitrite derived from the neurotoxic peptide.