Effect of sodium hydrosulfide on gene expression of intestinal epithelial cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE125342 | GEO | 2020/01/01
REPOSITORIES: GEO
Similar Datasets
Project description:Mitophagy is one of the most important cellular processes to ensure mitochondrial quality control, which aims to transport damaged, dysfunctional, or excess mitochondria for degradation and reuse. Here, we determined the function of AoAtg11 and AoAtg33, two orthologous autophagy-related proteins involved in yeast mitophagy, in the typical nematode-trapping fungus Arthrobotrys oligospora . Deletion of Aoatg11 and Aoatg33 impairs mitophagy, mitochondrial morphology and activity, autophagy,cell apoptosis, reactive oxygen species levels, lipid droplet accumulation, and endocytosis. These combined effects resulted in slow vegetative growth; reduced conidiation, trap formation, cell nucleus, and extracellular protease activity; increased susceptibility to the stress response; and arthrobotrisin production in the Δ Aoatg11 and Δ Aoatg33 mutants, compared with the wild-type strain. In addition, the absence of Aoatg11 caused an endoplasmic reticulum stress response. Transcriptome analysis revealed that many differentially expressed genes in the Δ Aoatg11 mutants were involved in various important cellular processes, such as lipid metabolism, the TCA cycle, mitophagy, nitrogen metabolism, endocytosis, and the MAPK signaling pathway. In conclusion, our study revealed that Aoatg11 and Aoatg33 mediate autophagy and mitophagy in A. oligospora , and provides a basis for elucidating the links between mitophagy and fungal vegetative growth, conidiation, and pathogenicity.
2022-09-09 | GSE212735 | GEO
Project description:The ubiquitous gasotransmitter hydrogen sulfide (H2S) has been recognised to play a crucial role in human health. However, a role for host H2S in pathogenesis has not yet been demonstrated. Using cystathionine -lyase (CSE) deficient mice, we demonstrated an unexpected role of H2S in Mtb pathogenesis. We showed that Mtb-infected CSE-/- mice survive longer than wild-type mice, and support reduced pathology and lower bacterial burdens in the lung, spleen and liver. Similarly, in vitro Mtb infection of macrophages resulted in reduced colony forming units (CFUs) in CSE-/-cells. Chemical complementation of infected wild-type and CSE-/-macrophages using the slow H2S releaser GYY3147 and the CSE inhibitor DL-propargylglycine demonstrated that H2S is the effector molecule regulating Mtb survival in macrophages. Furthermore, we demonstrate that CSE promotes an excessive innate immune response, suppresses the adaptive immune response and reduces circulating IL1β, IL-6, TNFα, and IFN-γ levels in response to Mtb infection. Notably, Mtb infected CSE-/- macrophages show increased flux through glycolysis and the pentose phosphate pathway thereby establishing a critical link between H2S and central metabolism. Our data suggest that excessive H2S produced by the infected wild type mice reduce HIF-1α levels, thereby suppressing glycolysis and production of IL-1β, IL-6 and IL-12, and increasing bacterial burden. Clinical relevance was demonstrated by the spatial distribution of H2S producing enzymes in human necrotic, non-necrotic and cavitary pulmonary TB lesions. In summary, CSE exacerbates TB pathogenesis by altering immunometabolism in mice and inhibiting CSE or modulating glycolysis are potential targets for host-directed TB control.
2020-04-06 | GSE143619 | GEO
Project description:Tumor-associated macrophages (TAMs) affect cancer progression and therapy. Ovarian carcinoma often metastasizes to the peritoneal cavity. Here, we found two peritoneal macrophage subsets in mice bearing ID8 ovarian cancer based on the Tim-4 (T-cell immunoglobulin and mucin domain containing 4) expression. Tim-4+ TAMs were embryonically originated and locally sustained while Tim-4- TAMs were replenished from circulating monocytes. Tim-4+ TAMs, but not Tim-4- TAMs, promoted tumor growth in vivo. Relative to Tim-4- TAMs, Tim-4+ TAMs manifested high oxidative phosphorylation and adapted mitophagy to alleviate oxidative stress. High levels of arginase-1 in Tim-4+ TAMs contributed to potent mitophagy activities via weakened mTORC1 activation due to low arginine resultant from arginase-1-mediated metabolism. Furthermore, genetic deficiency of autophagy element FIP200 resulted in Tim-4+ TAM loss via ROS-mediated apoptosis, and elevated T cell-immunity and ID8 tumor inhibition in vivo. Moreover, human ovarian cancer-associated CRIg (complement receptor of the Immunoglobulin superfamily) positive macrophages were transcriptionally, metabolically, and functionally similar to murine Tim-4+ TAMs. Thus, targeting CRIg+ (Tim-4+) TAMs may potentially treat ovarian cancer patients with peritoneal metastasis.
2020-09-09 | GSE157673 | GEO
Project description:Down syndrome (DS), a complex genetic disorder caused by chromosome 21 trisomy, is associated with mitochondrial dysfunction leading to the accumulation of damaged mitochondria. Here we report that mitophagy, a form of selective autophagy activated to clear damaged mitochondria is deficient in primary human fibroblasts derived from individuals with DS leading to accumulation of damaged mitochondria with consequent increases in oxidative stress. We identified two molecular bases for this mitophagy deficiency: PINK1/PARKIN impairment and abnormal suppression of macroautophagy. First, strongly downregulated PARKIN and the mitophagic adaptor protein SQSTM1/p62 delays PINK1 activation to impair mitophagy induction after mitochondrial depolarization by CCCP or antimycin A plus oligomycin. Secondly, mTOR is strongly hyper-activated, which globally suppresses macroautophagy induction and the transcriptional expression of proteins critical for autophagosome formation such as ATG7, ATG3 and FOXO1. Notably, inhibition of mTOR complex 1 (mTORC1) and complex 2 (mTORC2) using AZD8055 (AZD) restores autophagy flux, PARKIN/PINK initiation of mitophagy, and the clearance of damaged mitochondria by mitophagy. These results recommend mTORC1-mTORC2 inhibition as a promising candidate therapeutic strategy for Down Syndrome.
2019-06-22 | GSE126910 | GEO
Project description:Bladder cancer is one of the most common malignancy in the urinary tract with high recurrence and drug resistance in clinics. Alternative treatments from existing drugs might be a promising strategy. Nitazoxanide (NTZ), an FDA-approved antiprotozoal drug, has got increasingly noticed because of its favorable safety profile and antitumor potential, yet the effects in bladder cancer and underlying mechanisms remain poorly understood. Herein, we find that NTZ induces mitochondrial damage and mitophagy initiation through PINK1-generated phospho-ubiquitin(pS65-Ub) and autophagy receptor-mediated pathway even in the absence of Atg5/Beclin1. Meanwhile, NTZ inhibits lysosomal degradation activity, leading to mitophagy flux impairment at late stage. Mitochondrial reactive oxygen species (ROS) production is critical in this process, as eliminating ROS with N-acetylcysteine (NAC) efficiently inhibits PINK1 signaling-mediated mitophagy initiation and alleviates lysosomal dysfunction. Co-treatment with NTZ and autophagy inhibitor Chloroquine (CQ) to aggravate mitophagy flux impairment promotes NTZ-induced apoptosis, while alleviation of mitophagy flux impairment with ROS scavenger reduced cell death. Moreover, we also discover a similar signaling response in the 3D bladder tumor spheroid after NTZ exposure. In vivo study reveals a significant inhibition of orthotopic bladder tumors with no obvious systemic toxicity. Together, our results uncover the anti-tumor activities of NTZ with the involvement of ROS-mediated mitophagy modulation at different stages and demonstrate it as a potential drug candidate for fighting against bladder tumors.
2021-03-31 | GSE171129 | GEO
Project description:Intestinal microbial dysbiosis is associated with Crohn’s disease (CD). However, the mechanisms leading to the chronic mucosal inflammation that characterizes this disease remain unclear. To evaluate causality and mechanisms of disease, we conducted a systems level study of the interactions between the gut microbiota and host in new-onset pediatric patients. We report an altered host proteome in CD patients indicative of impaired mitochondrial functions. A downregulation of mitochondrial proteins implicated in H2S detoxification was observed, while the relative abundance of H2S microbial producers was increased. Network correlation analysis identified Atopobium parvulum as the central hub of H2S producers. Gnotobiotic and conventionalized colitis-susceptible interleukin-10-deficient (Il10-/-) mice demonstrated that A. parvulum induced colitis, a phenotype requiring the presence of the intestinal microbiota. Administration of bismuth, a H2S scavenger, prevented A. parvulum-induced colitis in Il10-/- mice. This study identified host-microbiota interactions that are disturbed in CD patients providing mechanistic insights on CD pathogenesis.
2016-09-29 | PXD002882 | Pride
Project description:Background: Lactobacillus plantarum is found in a variety of fermented foods and as such, consumed for centuries. Some strains are natural inhabitants of the human gastro-intestinal tract and like other Lactobacillus species, L. plantarum has been extensively studied for its immunomodulatory properties and its putative health-promoting effects (probiotic). Being the first line of host defense intestinal epithelial cells (IEC) are key players in the recognition and initiation of responses to gut microorganisms. Results: Using high-density oligonucleotide microarrays we examined the gene expression profiles of differentiated Caco-2 cells exposed to various doses of L. plantarum. In addition, the effects were correlated to monolayer permeability studies and measurement of lactic acid production. A transcriptional dose-dependent IEC response to L. plantarum was found. Incubation of Caco-2 with a low bacterial dose induced a specific response, not due to cytotoxicity or production of lactic acid, including modulation of cell cycle and cell signaling functions. Exposure of Caco-2 cells to larger amounts of bacteria, accompanied by the production of lactic acid and glucose depletion, provoked increased permeability and supposed non-specific defense responses. Conclusions: These results suggest that IEC are able to sense and react to the presence of gut bacteria. This study provides the first description of global transcriptional response of human IEC to a commensal lactic acid bacterium, and it shows the importance of choosing physiological bacterial doses to prevent the observation of non-specific host reactions. Caco-2 cells were exposed for 10h to Lactobacillus. Fourteen samples are analyzed: 4 control Caco-2, 4 Caco-2 exposed to a low dose (10) of Lactobacillus, 4 Caco-2 exposed to a medium dose (100) of Lactobacillus, 2 Caco-2 exposed to a high dose (1000) of Lactobacillus. All 14 RNA samples are labeled with Cy5 and hybridized to a common reference (undifferentiated Caco-2, untreated) RNA labeled with Cy3
2010-06-11 | E-GEOD-4325 | biostudies-arrayexpress
Project description:Serine protease inhibitor Kazal type 3 (Spink3) is a trypsin inhibitor in the pancreas. Spink3-/- pancreatic acinar cells are dead with excessive autophagy at birth (p0.5). To prove the role of nonapoptotic cell death with autophagy, we generated by transgenic technology the pancreas of Spink3-/-;XKI/+ mice contained both normal and dying acinar cells with autophagy. In this new mouse model, chronic inflammation occurred in the pancreas, indicating that some signals from nonapoptotic dead cell induce chronic inflammation in the pancreas. All samples were the pancreas at p0.5. Sample 1 and 2 are the pancreas from wild type (Spink3+/+, control) mice. Sample 3 and 4 are the pancreas from Spink3-/-, which all pancreatic acinar cells show induced nonapoptotic cell death with autophagy. Sample 5 and 6 are the pancreas from Spink3-/-XKI/+, about half acinar cells are normal, but other acinar cells show induced nonapoptotic cell death with autophagy.
2016-07-16 | E-GEOD-48946 | biostudies-arrayexpress
Project description:Hydrogen sulfide (H2S) is a signaling molecule that regulates essential plant processes, such as autophagy and responses to abiotic stresses. Although there is much information about the processes in which H2S is involved, the mechanism of action of H2S is still unclear. However, the posttranslational modification of cysteine residues, named persulfidation, is the main proposed mechanism. In this study, the role of H2S during drought that allows plant stress adaptation has been analyzed, with the focus on the underlying mechanism. H2S pretreatment before imposing drought on plants significantly improved phenotypic traits and decreased the content of biochemical and molecular drought stress markers. In addition, H2S regulated amino acid metabolism and repressed drought-induced degradation pathways, such as bulk autophagy and protein ubiquitination. The label-free quantitative proteomic analysis of plants growing under control and drought stress identified 887 proteins significantly different persulfidated between both conditions. Bioinformatic analyses revealed that the biological processes most enriched containing the proteins more persulfidated in drought corresponded to cellular response to oxidative stress, and hydrogen peroxide catabolism. In addition, protein degradation, abiotic stress responses, anthocyanin-containing compound biosynthetic process, and flavonoid biosynthesis were highlighted. On the contrary, the most enriched biological process containing proteins with lower levels of persulfidation in drought corresponded to the biosynthetic processes of glucosinolates and chlorophyll. Therefore, our findings emphasize the role of H2S as a promoter of enhanced tolerance to drought, enabling plants to respond more rapidly and efficiently after exposure to drought. Furthermore, the proteomic analysis supports the main role of protein persulfidation as the molecular mechanism of H2S to alleviate ROS accumulation and balance redox homeostasis under drought stress.
2023-10-24 | PXD039999 | Pride
Project description:Analysis of gene expression in Caco-2 intestinal epithelial cells stimulated with Bifidobacterium bifidum PRL2010. We used microarrays to investigate gene expression in intestinal epithelial cells in response to Bifidobacterium bifidum PRL2010, in particular genes involved in mucin pathways. Caco-2 cells were grown in transwell plates to 4 days post-confluence. Cells were then incubated for 2h and 4h with Bifidobacterium bifidum PRL2010. The experiment was performed in duplicate. Caco-2 RNA was extracted and hybridized to Affymetrix NuGO_Hs1a52018 arrays.
2010-10-01 | E-GEOD-21976 | biostudies-arrayexpress