1.Thiol redox barrier; local and systemic surveillance against stress and inflammatory diseases.
Yodoi J1, Tian H2, Masutani H3, Nakamura H3. Arch Biochem Biophys. 2016 Apr 1;595:88-93. doi: 10.1016/j.abb.2015.11.029.
A 12-kDa protein with redox-active dithiol in the active site -Cys-Gly-Pro-Cys-, human thioredoxin 1 (TRX) has demonstrated an excellent anti-inflammatory effect in various animal models. TRX is induced by various oxidative stress factors, including ultraviolet rays, radiation, oxidation, viral infections, ischemia reperfusion and anticancer agents, and are involved in the pathogenesis and progression of various diseases. We have demonstrated that systemic administration and transgenic overexpression of TRX is effective in a wide variety of in vivo inflammatory disease models, such as viral pneumonia, acute lung injury, chronic obstructive pulmonary disease, indomethacin-induced gastric injury, and dermatitis. Our recent studies indicate that topically applied TRX prevents skin inflammation via the inhibition of local formation of inflammatory cytokines and chemokines. These indicate that the activation of inflammasome in skin and mucosa may be regulated by TRX.
2.Manganism and Parkinson's disease: Mn(ii) and Zn(ii) interaction with a 30-amino acid fragment.
Remelli M1, Peana M2, Medici S2, Ostrowska M3, Gumienna-Kontecka E3, Zoroddu MA2. Dalton Trans. 2016 Mar 15;45(12):5151-61. doi: 10.1039/c6dt00184j.
A protected 30-amino acid fragment, Acetyl-SPDEKHELMIQLQKLDYTVGFCGDGANDCG-Amide, Acetyl-Ser-Pro-Asp-Glu-Lys-His-Glu-Leu-Met-Ile-Gln-Leu-Gln-Lys-Leu-Asp-Tyr-Thr-Val-Gly-Phe-Cys-Gly-Asp-Gly-Ala-Asn-Asp-Cys-Gly-Amide, encompassing the sequence from residues 1164 to 1193 in the encoded protein from Parkinson's disease gene Park9 (YPk9), was studied for manganese and zinc binding. Manganese exposure is considered to be an environmental risk factor connected to PD and PD-like syndrome. Research into the genetic and environmental risk factors involved in disease susceptibility has recently uncovered a link existing between Park9 and manganese. It seems that manganese binding to Park9 (YPk9) protein is involved in the detoxification mechanism exerted by this protein against manganese toxicity. In this study, we used potentiometric, mono- and bi-dimensional (TOCSY, HSQC) NMR, EPR and ESI-MS measurements to analyze complex formation and metal binding sites in the peptide fragment.
3.Tc-99m Glu-Cys-Gly-His-Gly-Lys (ECG-HGK), a novel Tc-99m labeled hexapeptide for molecular tumor imaging.
Kim DW1,2, Kim MH1, Kim CG1. J Labelled Comp Radiopharm. 2016 Mar;59(3):124-8. doi: 10.1002/jlcr.3378. Epub 2016 Feb 9.
Domain 5 of kinin-free high molecular weight kininogen inhibits the adhesion of many tumor cell lines, and it has been reported that the histidine-glycine-lysine (HGK)-rich region might be responsible for inhibition of cell adhesion. The authors developed HGK-containing hexapeptide, glutamic acid-cysteine-glycine (ECG)-HGK, and evaluated the utility of Tc-99m ECG-HGK for tumor imaging. Hexapeptide, ECG-HGK was synthesized using Fmoc solid-phase peptide synthesis. Radiolabeling efficiency was evaluated. The uptake of Tc-99m ECG-HGK within HT-1080 cells was evaluated in vitro. In HT-1080 tumor-bearing mice, gamma imaging and biodistribution studies were performed. The complexes Tc-99m ECG-HGK was prepared in high yield. The uptake of Tc-99m ECG-HGK within the HT-1080 tumor cells had been demonstrated by in vitro studies. The gamma camera imaging in the murine model showed that Tc-99m ECG-HGK was accumulated substantially in the HT-1080 tumor (tumor-to-muscle ratio = 5.
4.Homocysteinemia control by cysteine in cerebral vascular patients after methionine loading test: evidences in physiological and pathological conditions in cerebro-vascular and multiple sclerosis patients.
Ulivelli M1,2, Priora R2, Di Giuseppe D2, Coppo L2, Summa D2, Margaritis A2, Frosali S2, Bartalini S1,2, Martini G3, Cerase A4, Di Simplicio P5. Amino Acids. 2016 Mar 11. [Epub ahead of print]
The toxicity risk of hyperhomocysteinemia is prevented through thiol drug administration which reduces plasma total homocysteine (tHcy) concentrations by activating thiol exchange reactions. Assuming that cysteine (Cys) is a homocysteinemia regulator, the hypothesis was verified in healthy and pathological individuals after the methionine loading test (MLT). The plasma variations of redox species of Cys, Hcy, cysteinylglycine, glutathione and albumin (reduced, HS-ALB, and at mixed disulfide, XSS-ALB) were compared in patients with cerebral small vessels disease (CSVD) (n = 11), multiple sclerosis (MS) (n = 12) and healthy controls (n = 11) at 2-4-6 h after MLT. In MLT-treated subjects, the activation of thiol exchange reactions provoked significant changes over time in redox species concentrations of Cys, Hcy, and albumin. Significant differences between controls and pathological groups were also observed. In non-methionine-treated subjects, total Cys concentrations, tHcy and thiol-protein mixed disulfides (CSS-ALB, HSS-ALB) of CSVD patients were higher than controls.