Search results for "Stein"

γ-Glutamyl cysteine suppresses TNF-α up-regulation via protein phosphatases in acute pancreatitis

2016

Cognate HLA absence in trans diminishes human NK cell education

2016

NK cells are innate lymphocytes with protective functions against viral infections and tumor formation. Human NK cells carry inhibitory killer cell Ig-like receptors (KIRs), which recognize distinct HLAs. NK cells with KIRs for self-HLA molecules acquire superior cytotoxicity against HLA– tumor cells during education for improved missing-self recognition. Here, we reconstituted mice with human hematopoietic cells from donors with homozygous KIR ligands or with a mix of hematopoietic cells from these homozygous donors, allowing assessment of the resulting KIR repertoire and NK cell education. We found that co-reconstitution with 2 KIR ligand–mismatched compartments did not alter the frequenc…

Systemic redox biomarkers and their relationship to prognostic risk markers in autosomal dominant polycystic kidney disease and IgA nephropathy.

2017

Abstract Background Oxidative stress is evident from an early stage in chronic kidney disease (CKD). Therefore, we investigated redox biomarkers in polycystic kidney disease (ADPKD) and IgA nephropathy (IGAN). Methods This is a case-control study with three groups: ADPKD (n = 54), IGAN (n = 58) and healthy controls (n = 86). The major plasma aminothiols with their redox species were examined: homocysteine (Hcy), cysteinglycine (CG), cysteine (Cys) and glutathione (GSH). The redox ratio was the ratio of reduced free and oxidized aminothiols in plasma. We investigated malonedialdehyde (MDA) and advanced oxidation protein products (AOPP), and ten single nucleotide polymorphisms of antioxidant …

Homocysteine Induces Apoptosis of Human Umbilical Vein Endothelial Cells via Mitochondrial Dysfunction and Endoplasmic Reticulum Stress

2017

Homocysteine- (Hcy-) induced endothelial cell apoptosis has been suggested as a cause of Hcy-dependent vascular injury, while the proposed molecular pathways underlying this process are unclear. In this study, we investigated the adverse effects of Hcy on human umbilical vein endothelial cells (HUVEC) and the underlying mechanisms. Our results demonstrated that moderate-dose Hcy treatment induced HUVEC apoptosis in a time-dependent manner. Furthermore, prolonged Hcy treatment increased the expression of NOX4 and the production of intracellular ROS but decreased the ratio of Bcl-2/Bax and mitochondrial membrane potential (MMP), resulting in the leakage of cytochrome c and activation of caspa…

Clearing Amyloid-β through PPARγ/ApoE Activation by Genistein is a Treatment of Experimental Alzheimer’s Disease

2016

Amyloid-b (Ab) clearance from brain, which is decreased in Alzheimer's disease, is facilitated by apolipoprotein E (ApoE). ApoE is upregulated by activation of the retinoid X receptor moiety of the RXR/PPAR dimeric receptor. As we have previously demonstrated, estrogenic compounds, such as genistein, have antioxidant activity, which can be evidenced by increased expression of manganese superoxide dismutase (MnSOD). Furthermore, genistein is a non-toxic, well-tested, and inexpensive drug that activates PPARg receptor. We isolated and cultured cortical astrocytes from dissected cerebral cortices of neonatal mice (C57BL/6 J). Preincubation with genistein (5 mM) for 24 hours, prior to the addit…

Clearing Amyloid-β Through PPARγ/ApoE Activation by Genistein is an Experimental Treatment of Alzheimer's Disease

2016

Amyloid-β (Aβ) clearance from brain, which is decreased in Alzheimer’s disease, is facilitated by apolipoprotein E. Apo E is up-regulated by activation of the retinoid X receptor moiety of the RXR/PPARγ dimeric receptor. Genistein, a non-toxic, well tested and inexpensive drug has a multifaceted protective effect: antioxidant (because it stimulates the expression of antioxidant genes), anit-inflammatory and stimulator of activates the PPARγ receptor, which results in increased expression of ApoE. Treatment of an Alzheimer’s mouse model with genistein results in a remarkable and rapid improvement in various parameters of cognition, such as hippocampal learning, recognition memory, implicit m…

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…

Virus-encoded microRNA contributes to the molecular profile of EBV-positive Burkitt lymphomas

2015

Burkitt lymphoma (BL) is an aggressive neoplasm characterized by consistent morphology and phenotype, typical clinical behavior and distinctive molecular profile. The latter is mostly driven by the MYC over-expression associated with the characteristic translocation (8;14) (q24; q32) or with variant lesions. Additional genetic events can contribute to Burkitt Lymphoma pathobiology and retain clinical significance. A pathogenetic role for Epstein-Barr virus infection in Burkitt lymphomagenesis has been suggested; however, the exact function of the virus is largely unknown. In this study, we investigated the molecular profiles (genes and microRNAs) of Epstein-Barr virus-positive and -negative…

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…