Project description:Epidemiological studies link exposure to mercury with autoimmune disease. Unfortunately, in spite of considerable effort, no generally accepted mechanistic understanding of how mercury actually functions with respect to the etiology of autoimmune disease is currently available. Nevertheless, autoimmune disease often arises because of defective B cell signaling. Because B cell signaling is dependent on phosphorylation cascades, in this report, we have focused on how mercury intoxication alters phosphorylation of B cell proteins in antigen-non stimulated (tonic) mouse splenic B cells. Specifically, we utilized mass spectrometric techniques to conduct a comprehensive unbiased global analysis of the effect of mercury on the entire B cell phosphoproteome. We found that the effects were pleotropic in the sense that large numbers of pathways were impacted. However, confirming our earlier work, we found that the B cell signaling pathway stood out from the rest, in that phosphoproteins which had sites which were affected by mercury, exhibited a much higher degree of connectivity, than components of other pathways. Further analysis showed that many of these BCR pathway proteins had been previously linked to autoimmune disease. Finally, dose response analysis of these BCR pathway proteins showed STIM1_S575, and NFAT2_S259 are the two most mercury sensitive of these sites. Because STIM1_S575 controls the ability of STIM1 to regulate internal Ca2+, we speculate that STIM1 may be the initial point of disruption, where mercury interferes with B cell signaling leading to systemic autoimmunity, with the molecular effects pleiotropically propagated throughout the cell by virtue of Ca2+ dysregulation.
Project description:Gold salts has been used in the treatment of rheumatoid arthritis but has been replaced by biologicals such as TNF-alpha inhibitors. The mechanisms behind the anti-inflammatory effect of metallic gold ions are still unknown, however, recent data showed that charged gold atoms are released from pure metallic gold implants by macrophages via a dissolucytosis membrane, and that gold ions are taken up by local macrophages, mast cells and to some extent fibroblasts. These current findings offer new treatment options for metallic gold and deeper understanding of the effect of metallic gold on key inflammatory cells as macrophages are essential. In the present study the impact of phagocytised gold ions on the global gene expression profile of the human monocytic cell line THP-1 was investigated, using microarray analysis comprising approximately 20,000 genes. The gene expression data was confirmed by measurement of three secreted proteins. A unique gene expression signature of dissolucytotic macrophages that had taken up gold ions was demonstrated. A large number of regulated genes were functionally related to immunomodulation/protection. Gold ion uptake into macrophages induced downregulation of central inflammatory cytokines as TNF-alpha, IL-32 and CD28. The data obtained in this study offer new insights into the mode of action of gold ions and suggest a future role of metallic gold as implants or topical applications in treating inflammation. To determine the effect of gold phagocytosis on global gene expression
Project description:Gastric Cancer (GC) is one of the most serious cancers with high incidence and mortality all over the world. Chemotherapy hadn’t led to desirable effect and targeted therapy brings about a new stage to cancer treatment. Ramucirumab is the first FDA-approved monotherapy for advanced gastric cancer. It is well known that gold nanorod, a nontoxic biocompatible nanomaterial, is an especially promising candidate for cancer theranostic. In this study, Ramucirumab (Ab) were first modified by gold nanoparticles to enhance uptake efficiency. The simple Nano-delivery system had taken perfect aggregation effect in vivo even better than 5-fold Ab treatment. Gold nanomaterials, especially gold nanorod (AuNR), could induce direct cytotoxic effect to cancer cell in the presence of Ab, while Ab or gold nanoparticle themselves couldn’t lead to such direct killing effect even at an extremely high concentration. Transcriptomic and proteomic analyses revealed the mechanism of this direct cytotoxicity.
2021-08-06 | GSE181369 | GEO
Project description:Mercury-resistant bacteria isolated from soil samples contaminated with mercury released from artisanal gold processing sites in Sukabumi, Indonesia
| PRJNA1045334 | ENA
Project description:Mercury toxic effect in microbial population
Project description:Heavy metals have been postulated as significant nitrification inhibitor in wastewater treatment plant. The effect of heavy metals such as Cd2+, Cu2+ and Hg2+ to nitrifying bacterium, Nitrosomonas europaea, was studied in pseudo-steady state batch reactor. Under incubation of Nitrosomonas europaea with 1 ?M CdCl2 for 1 hour, transcripts for 66 of 2460 genes were found at high level, yet transcripts of 50 genes were found at low level. Mercury resistance genes (merACDPT) showed 277-fold up regulation. Keywords: cadmium, stress response, global transcription, mercury resistance genes, merA,
Project description:Gold salts has been used in the treatment of rheumatoid arthritis but has been replaced by biologicals such as TNF-alpha inhibitors. The mechanisms behind the anti-inflammatory effect of metallic gold ions are still unknown, however, recent data showed that charged gold atoms are released from pure metallic gold implants by macrophages via a dissolucytosis membrane, and that gold ions are taken up by local macrophages, mast cells and to some extent fibroblasts. These current findings offer new treatment options for metallic gold and deeper understanding of the effect of metallic gold on key inflammatory cells as macrophages are essential. In the present study the impact of phagocytised gold ions on the global gene expression profile of the human monocytic cell line THP-1 was investigated, using microarray analysis comprising approximately 20,000 genes. The gene expression data was confirmed by measurement of three secreted proteins. A unique gene expression signature of dissolucytotic macrophages that had taken up gold ions was demonstrated. A large number of regulated genes were functionally related to immunomodulation/protection. Gold ion uptake into macrophages induced downregulation of central inflammatory cytokines as TNF-alpha, IL-32 and CD28. The data obtained in this study offer new insights into the mode of action of gold ions and suggest a future role of metallic gold as implants or topical applications in treating inflammation.