Biology subjects

Diemer, H.

Publications and source records attributed to Diemer, H..

5 recordsLinked to original sources

bioRxiv2025

Effects of manganese dioxide on macrophages under different exposure schemes

Manganese dioxide is a material that is more and more used in its particular form, for many industrial applications such as chemical catalysis or for batteries. Thus, workers can be exposed to this particulate chemical. It is known that overexposure to manganese leads to a brain disease called manganism. However, manganese is also known to impact the pulmonary function, which is important as pulmonary exposure is of prime importance for workers. We thus investigated the effects of manganese dioxide on macrophages, i.e. the scavenger cells that take particulates in charge in our bodies. To this purpose, we used a combination of proteomic and targeted approaches, in order to obtain a wide view of the cellular responses to manganese dioxide. We also used a repeated exposure mode, in order to better mimic occupational exposure. Our results point out the fact that manganese oxide nanoparticles are rather toxic for macrophages and induce mitochondrial dysfunction, oxidative stress and a pro-inflammatory response. Environmental significanceManganese dioxide is more and more used in batteries, so that workers in batteries factories are exposed to this metallic oxide. As always for particulate materials, macrophages are the first line of defense of the organism. We thus investigated the effects of manganese dioxide on macrophages, using a repeated exposure scheme to mimic occupational exposure, and the effects were documented by a combination of proteomic and targeted approaches. The functional effects include mitochondrial dysfunction, oxidative stress and inflammation.

pharmacology and toxicology↗

bioRxiv2025

Beyond the ink: cellular and molecular effects of iron-based pigments on macrophages

As ochre, iron oxide is among the most ancient pigments used by mankind for different purposes, including tattooing as demonstrated on tattoed mummies. Iron oxides are still used in tattooing nowadays and especially in dermopigmentation, an area of medical tattoing aiming at restoring the color of skin. This ancient use of iron oxide does not mean that it has no effect on cells, and especially on macrophages, the cells that maintain pigments particles on site in tattoos. We thus investigated in vitro the delayed/sustained effects of iron oxide pigments on macrophages, i.e. the effects occurring a few days after the exposure to pigments, on pigments-loaded macrophages but in a pigment-free medium, mimicking the status of tattooed skin after all the pigment particles have been captured. By combining proteomic and targeted approaches, we determined that red iron oxide (but not black iron oxide) induces perturbations in mitochondria, altering the mitochondrial transmembrane potential. Red iron oxide also induces oxidative stress and the secretion of pro-inflammatory cytokines such as interleukin 6 and tumor necrosis factor. Thus, red iron oxide induces adverse effects on macrophages that may persist over time, owing to its low intracellular dissolution.

immunology↗

bioRxiv2025

Identification of uranyl-binding proteins in Arabidopsis thaliana cells exposed to uranium: Insights from a metalloproteomic analysis and characterization of Glycine-Rich RNA-binding Protein 7 (GRP7)

Uranium (U) is a naturally occurring radionuclide, chemotoxic for living organisms. To identify proteins that could be cellular targets for U in plants, we used metalloproteomic approaches combining column chromatographic fractionation analyses, protein identification by high-resolution mass spectrometry shotgun proteomics, and metal quantification by induced coupled plasma mass spectrometry. We identified 57 candidate proteins for uranyl (U(VI)) binding in cultured Arabidopsis thaliana cells. One of these proteins, the Glycine-Rich RNA-binding Protein 7 (GRP7) is a RNA-binding protein involved in various developmental processes and responses to biotic and abiotic stress. Recombinant GRP7 was purified from overproducing bacteria and subjected to further biochemical characterization. First, we showed that GRP7 binds U(VI) with a 1:2 (protein:metal) stoichiometry in vitro. Next, we analyzed its structural properties by solution-state nuclear magnetic resonance spectroscopy. This allowed us to gain insight into the molecular dynamics of the protein-metal interaction and to identify residues involved in U(VI)-binding in the two sites. Finally, we observed that U(VI) binding interferes with nucleic acid binding to the protein RNA-binding domain, suggesting that U(VI) binding to GRP7 contributes to U toxicity in plants. HIGHLIGHTSO_LI57 candidate uranyl-binding proteins were identified from Arabidopsis cells exposed to uranyl, of which the RNA-binding protein GRP7. C_LIO_LIIn vitro, recombinant GRP7 binds 2 uranyl ions within the RNA recognition motif domain. C_LIO_LIAmino acid residues involved in uranyl binding in both binding sites were identified. C_LIO_LICompetition between specific oligonucleotide and uranyl for binding suggests the implication of GRP7 in uranium toxicity, as a cellular target. C_LI

biochemistry↗

bioRxiv2024

Biobased, Biodegradable but not bio-neutral: about the effects of polylactic acid nanoparticles on macrophages

Plastics are persistent pollutants, because of their slow degradation, which suggests that they may lead to cumulative and/or delayed adverse effects due to their progressive accumulation over time. Macroplastics produced by human activity are released in the environment, where they degrade into micro and nanoplastics that are very easily uptaken by a wide variety of organisms, including humans. Microplastics and nanoplastics being particulates, they are handled in the body by specialized cells such as macrophages (or their evolutionary counterparts), where they can elicit a variety of responses. One solution to alleviate the problems due to biopersistence, such as accumulation over life, would be to use biodegradable plastics. One of the emerging biodegradable plastics being polylactide, we decided to test the responses of macrophages to polylactide nanoparticles, using a combination of untargeted proteomics and targeted validation experiments. Proteomics showed important adaptive changes in the proteome in response to exposure to polylactide nanoparticles. These changes affected for example mitochondrial, cytoskeletal and lysosomal proteins, but also proteins implicated in immune functions or redox homeostasis. Validation experiments showed that many of these changes were homeostatic, with no induced oxidative stress and no gross perturbation of the mitochondrial function. However, polylactide particles altered the immune functions such as phagocytosis (-20%) or cytokine production (2-fold increase for TNF production), which may translate into a decreased ability to macrophages to respond to bacterial infections. Furthermore, polylactide particles also induced moderate cross-toxicity with some quinones such as phenanthrene quinone, a combustion by-product that is a suspected carcinogen.

pharmacology and toxicology↗

bioRxiv2024

E cadherin appears to be an essential on/off switch for initiating bile canaliculi formation

The mechanisms underlying cell polarization are fundamental in biology, yet they are not fully understood. This is particularly true for hepatocytes, which exhibit a complex polarization, enabling the formation of the bile canaliculi (BCs) network that is essential for liver excretion functions. To identify key proteins involved in hepatocyte polarization and BC formation, we performed a proteomic approach to compare the human hepatocyte cell line HepG2 to its sub clone HepG2/C3A which shows much greater efficiency in forming mature BCs. We localized LimA1 and Espin to the BC for the first time, suggesting their important role there, and confirmed the presence of NHE-RF1. Using a protein repression strategy directed against selected proteins, we highlighted the essential role of E cadherin in the initiation of BC formation. Our data showed, for the first time, that in absence of E cadherin, hepatocytes lose their ability to form BCs.

cell biology↗