Search results for "Cysteine"
showing 10 items of 550 documents
Oxidative stress modulates rearrangement of endoplasmic reticulum-mitochondria contacts and calcium dysregulation in a Friedreich's ataxia model
2020
Friedreich ataxia (FRDA) is a neurodegenerative disorder characterized by neuromuscular and neurological manifestations. It is caused by mutations in the FXN gene, which results in loss of the mitochondrial protein frataxin. Endoplasmic Reticulum-mitochondria associated membranes (MAMs) are inter-organelle structures involved in the regulation of essential cellular processes, including lipid metabolism and calcium signaling. In the present study, we have analyzed in both, unicellular and multicellular models of FRDA, calcium management and integrity of MAMs. We observed that function of MAMs is compromised in our cellular model of FRDA, which was improved upon treatment with antioxidants. I…
Progranulin overexpression in sensory neurons attenuates neuropathic pain in mice: Role of autophagy
2016
Peripheral or central nerve injury is a frequent cause of chronic pain and the mechanisms are not fully understood. Using newly generated transgenic mice we show that progranulin overexpression in sensory neurons attenuates neuropathic pain after sciatic nerve injury and accelerates nerve healing. A yeast-2-hybrid screen revealed putative interactions of progranulin with autophagy-related proteins, ATG12 and ATG4b. This was supported by colocalization and proteomic studies showing regulations of ATG13 and ATG4b and other members of the autophagy network, lysosomal proteins and proteins involved in endocytosis. The association of progranulin with the autophagic pathway was functionally confi…
Exploration of Fas S-Nitrosylation by the Biotin Switch Assay
2017
International audience; S-nitrosylation is the covalent attachment of nitric oxide radical to the thiol side chain of cysteine. The death receptor Fas/CD95 can be S-nitrosylated in cancer cell lines by NO donors or iNOS activation. This posttranslational modification (PTM) induces Fas aggregation into lipid rafts and enhances FasL-mediated signaling and apoptosis. In this report, we describe the detection of Fas S-nitrosylation by the most commonly used method, the biotin switch assay (BSA) technique, that allows the detection of this very labile covalent modification in cells or tissues. Briefly, this technique relies on the ability of ascorbate to reduce the covalent bond between the NO r…
The potential of cystatin C as a predictive biomarker in breast cancer
2020
Breast cancer (BCa) is the leading cause of cancer-related deaths among women. Numerous efforts are being directed toward identifying novel tissue and/or circulating molecular markers that may help clinicians in detecting early-stage BCa patients and in providing an accurate estimation of the prognosis and prediction of response to clinical treatments. In this setting, emerging evidence has indicated Cystatin C (Cyst C), as the most potent endogenous inhibitor of cysteine cathepsins, as a possible useful marker in the clinical management of BCa patients.This review analyzes the results of emerging studies underpinning a potential clinical role of Cyst C, as additional marker in BCa.Cyst C e…
Development of Novel Peptide-Based Michael Acceptors Targeting Rhodesain and Falcipain-2 for the Treatment of Neglected Tropical Diseases (NTDs)
2017
This paper describes the development of a class of peptide-based inhibitors as novel antitrypanosomal and antimalarial agents. The inhibitors are based on a characteristic peptide sequence for the inhibition of the cysteine proteases rhodesain of Trypanosoma brucei rhodesiense and falcipain-2 of Plasmodium falciparum. We exploited the reactivity of novel unsaturated electrophilic functions such as vinyl-sulfones, -ketones, -esters, and -nitriles. The Michael acceptors inhibited both rhodesain and falcipain-2, at nanomolar and micromolar levels, respectively. In particular, the vinyl ketone 3b has emerged as a potent rhodesain inhibitor (k2nd = 67 × 106 M-1 min-1), endowed with a picomolar b…
Cysteine, glutathione and a new genetic code: biochemical adaptations of the primordial cells that spread into open water and survived biospheric oxy…
2019
Abstract Life most likely developed under hyperthermic and anaerobic conditions in close vicinity to a stable geochemical source of energy. Epitomizing this conception, the first cells may have arisen in submarine hydrothermal vents in the middle of a gradient established by the hot and alkaline hydrothermal fluid and the cooler and more acidic water of the ocean. To enable their escape from this energy-providing gradient layer, the early cells must have overcome a whole series of obstacles. Beyond the loss of their energy source, the early cells had to adapt to a loss of external iron-sulfur catalysis as well as to a formidable temperature drop. The developed solutions to these two problem…
In silico drug discovery of major metabolites from spices as SARS-CoV-2 main protease inhibitors
2020
Coronavirus Disease 2019 (COVID-19) is an infectious illness caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), originally identified in Wuhan, China (December 2019) and has since expanded into a pandemic. Here, we investigate metabolites present in several common spices as possible inhibitors of COVID-19. Specifically, 32 compounds isolated from 14 cooking seasonings were examined as inhibitors for SARS-CoV-2 main protease (Mpro), which is required for viral multiplication. Using a drug discovery approach to identify possible antiviral leads, in silico molecular docking studies were performed. Docking calculations revealed a high potency of salvianolic acid A and curcu…
Prooxidative chain transfer activity by thiol groups in biological systems
2020
Cysteine is arguably the best-studied biological amino acid, whose thiol group frequently participates in catalysis or ligand binding by proteins. Still, cysteine's unusual biological distribution has remained mysterious, being strikingly underrepresented in transmembrane domains and on accessible protein surfaces, particularly in aerobic life forms (“cysteine anomaly”). Noting that lipophilic thiols have been used for decades as radical chain transfer agents in polymer chemistry, we speculated that the rapid formation of thiyl radicals in hydrophobic phases might provide a rationale for the cysteine anomaly. Hence, we have investigated the effects of dodecylthiol and related compounds in i…
Bioelectrochemical monitoring of soluble guanylate cyclase inhibition by the natural β-carboline canthin-6-one
2017
Abstract The inhibition of soluble guanylate cyclase (sGC) by canthin-6-one alkaloid ( L1 ) is presented and the mechanism of deactivation is studied using solution phase and voltammetry of microparticles methodologies. Possible inhibition pathways: oxidation of Fe 2+ to Fe 3+ coupled to reduction of the naphthyridone motif present by the canthin-6-one and coordinating or reacting of L1 with cysteine units of sGC, are balanced.
Nuclear Translocation of RELB Is Increased in Diseased Human Liver and Promotes Ductular Reaction and Biliary Fibrosis in Mice.
2019
Background & Aims Cholangiocyte proliferation and ductular reaction contribute to the onset and progression of liver diseases. Little is known about the role of the transcription factor nuclear factor-κB (NF-κB) in this process. We investigated the activities of the RELB proto-oncogene NF-κB subunit in human cholangiocytes and in mouse models of liver disease characterized by a ductular reaction. Methods We obtained liver tissue samples from patients with primary sclerosing cholangitis, primary biliary cholangitis, hepatitis B or C virus infection, autoimmune hepatitis, alcoholic liver disease, or without these diseases (controls) from a tissue bank in Germany. Tissues were analyzed by immu…