Biology subjects

Deiter, C.

Publications and source records attributed to Deiter, C..

4 recordsLinked to original sources

bioRxiv2024

Reduction of chemokine CXCL9 expression by omega-3 fatty acids via ADP-ribosylhydrolase ARH3 in MIN6 insulin-producing cells

Type 1 diabetes (T1D) results from the autoimmune destruction of the insulin producing {beta} cells of the pancreas. Omega-3 fatty acids protect {beta} cells and reduce the incident of T1D. However, how omega-3 fatty acids act on {beta} cells is not well understood. We have shown that omega-3 fatty acids reduce pro-inflammatory cytokine-mediated {beta}-cell apoptosis by upregulating the expression of the ADP-ribosylhydrolase ARH3. Here, we further investigate the {beta}-cell protection mechanism by ARH3 by performing siRNA of its gene Adprhl2 in MIN6 insulin-producing cells followed by treatment with a cocktail of the pro-inflammatory cytokines IL-1{beta} + IFN-{gamma} + TNF-, and proteomics analysis. ARH3 regulated proteins from several pathways related to the nucleus (splicing, RNA surveillance and nucleocytoplasmic transport), mitochondria (metabolic pathways) and endoplasmic reticulum (protein folding). ARH3 also regulated the levels of cytokine-signaling proteins related to the antigen processing and presentation, and chemokine-signaling pathway. We further studied the role of ARH in regulating the chemokine CXCL9. We confirmed that ARH3 reduces the cytokine-induced expression of CXCL9 by ELISA. We also found that CXCL9 expression is regulated by omega-3 fatty acids. In conclusion, we showed that omega-3 fatty acids regulate CXCL9 expression via ARH3, which might have a role in protecting {beta} cells from immune attack and preventing T1D development.

cell biology↗

bioRxiv2023

Convolutional neural network approach for the automated identification of in cellulo crystals

In cellulo crystallization is a rarely occurring event in nature. Recent advances, making use of heterologous overexpression, can promote the intracellular formation of protein crystals, but new tools are required to detect and to characterize these targets in the complex cell environment. In the present work we make use of Mask R-CNN, a Convolutional Neural Network (CNN) based instance segmentation method, for the identification of either single or multi-shaped crystals growing in living insect cells, using conventional bright field images. The algorithm can be rapidly adapted to recognize different targets, with the aim to extract relevant information to support a semi-automated screening pipeline, with the purpose to aid in the development of the intracellular protein crystallization approach.

biophysics↗

bioRxiv2020

The role of islet lipid composition remodeling in regulation of beta-cell death via ADP-ribosyl-acceptor glycohydrolase ARH3 signaling in insulitis

Lipids have been implicated as mediators of insulitis and {beta}-cell death in type 1 diabetes development, but the mechanisms underlying this association are poorly understood. Here, we investigated the changes in islet/{beta}-cell lipid composition using three models of insulitis: human islets and EndoC-{beta}H1 {beta}-cells treated with the cytokines IL-1{beta} and IFN-{gamma}, and islets from non-obese diabetic mice. Across all three models, lipidomic analyses showed a consistent change in abundance of the lysophosphatidylcholine, phosphatidylcholine and triacylglycerol species. We also showed that lysophosphatidylcholine and its biosynthetic enzyme PLA2G6 are enriched in murine islets. We determined that the ADP-ribosyl-acceptor glycohydrolase ARH3 is regulated by cytokines downstream of PLA2G6, which in turn regulates proteins involved in apoptosis, lipid metabolism, antigen processing and presentation and chemokines. ARH3 reduced cytokine-induced apoptosis, which may represent a negative feedback mechanism. Overall, these data show the importance of lipid metabolism in regulating {beta}-cell death in type 1 diabetes. HighlightsO_LILipidomics of 3 insulitis models revealed commonly regulated lipid classes. C_LIO_LIIdentification of 35 proteins regulated by cytokines via PLA2G6 signaling. C_LIO_LIARH3 reduces cytokine-induced apoptosis via PLA2G6 regulation. C_LIO_LIARH3 regulates the levels of proteins related to insulitis and type 1 diabetes. C_LI

systems biology↗

bioRxiv2019

Latent Toxoplasma gondii infection increases soluble mutant huntingtin and promotes neurodegeneration in the YAC128 mouse model of Huntington's disease

Toxoplasma gondii causes a prevalent neuroinvasive protozoal pathogen that in immune competent individuals results in latent infection characterized by intra-cellular parasite cysts in brain. Despite life-long infection, the role of latent toxoplasmosis on chronic neurodegenerative processes is poorly understood. Huntingtons disease (HD) is a progressive neurodegenerative disorder caused by a dominant CAG repeat expansion in the huntingtin gene (HTT) that results in the expression and accumulation of mutant huntingtin protein (mHTT). The mutant HD gene is fully penetrant. However, there is significant variability in disease progression that is in part explained by as yet unidentified environmental factors. The kynurenine pathway of tryptophan metabolism (KP) is an inflammatory pathway and its activation is implicated in HD pathogenesis. KP upregulation also occurs in response to infection with Toxoplasma gondii suggesting that the latent infection may promote HD. We discovered that mice on the FVB/NJ background develop latent toxoplasmosis following infection with the ME49 strain of T. gondii. This finding enabled us to address the hypothesis that latent toxoplasmosis potentiates disease in the YAC128 mouse model of HD, as these mice are maintained on the FVB/NJ background. Wild-type and HD mice were infected at 2-months of age. During the 10-month follow-up, infection had adverse effects on mice of both genotypes. However, YAC128 HD mice demonstrated specific vulnerability to latent toxoplasmosis, as demonstrated by the presence of increased striatal degeneration, high levels of the blood neurodegeneration marker neurofilament light protein, and elevated brain soluble mHTT. Our studies have uncovered a novel HD-infection interaction in mice that provides insights into the large variability of the human HD phenotype.

neuroscience↗