Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Protective impact on the apoptotic pathway by suppressing DMT1 during inflammatory stress

ABSTRACT: We performed phosphoproteomics using our sequential enrichment strategy of mRNA, protein, and phosphopeptides, which enabled us to explore the concurrent molecular events in the same sample and at the same time in normal and DMT1 silencing insulin-producing β-cells stimulated by siRNAs.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Rattus Norvegicus (rat) Mus Musculus (mouse)

SUBMITTER: Taewook Kang

LAB HEAD: Martin R. Larsen

PROVIDER: PXD017216 | Pride | 2021-08-10

REPOSITORIES: Pride

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	DMT1KD_Phosphoproteome.msf	Msf
	DMT1KD_Proteome.msf	Msf
	Replicate1_Flowthrough_1.raw	Raw
	Replicate1_Flowthrough_10.raw	Raw
	Replicate1_Flowthrough_11.raw	Raw

Items per page:

1 - 5 of 108

Publications

Divalent Metal Transporter 1 Knock-Down Modulates IL-1β Mediated Pancreatic Beta-Cell Pro-Apoptotic Signaling Pathways through the Autophagic Machinery.

Kang Taewook T Huang Honggang H Mandrup-Poulsen Thomas T Larsen Martin R MR

International journal of molecular sciences 20210727 15

Pro-inflammatory cytokines promote cellular iron-import through enhanced divalent metal transporter-1 (DMT1) expression in pancreatic β-cells, consequently cell death. Inhibition of β-cell iron-import by DMT1 silencing protects against apoptosis in animal models of diabetes. However, how alterations of signaling networks contribute to the protective action of DMT1 knock-down is unknown. Here, we performed phosphoproteomics using our sequential enrichment strategy of mRNA, pr ...[more]

PMID: 34360779

Similar Datasets

Label Free Quantification Mass Spectrometry Identifies Protein Markers of Chemoresistance in Serous Ovarian Cancer

Project description:Ovarian cancer is still the most lethal gynecological cancer, despite advances in patients’ strati-fication and treatment. Only about 80% of patients respond to the first line of treatment and many suffer a relapse with a treatment resistant disease. Here, we have identified three potential markers for chemoresistance using primary tumour samples. Moreover, we have shown their concurrent regulation in a chemoresistant cell line. This implies those cells as a useful model to study chemoresistance and to test novel drugs.

2023-05-10 | PXD033785 | Pride

Conversion of Osteoclasts into Bone-Protective, Tumor-Suppressing Cells.

Project description:Osteoclasts are a driver of a vicious bone-destructive cycle with breast cancer cells. Here, we examined whether this vicious cycle can be altered into a beneficial one by activating Wnt signaling with its activating agent, BML284. The conditioned medium, derived from Wnt-activated RAW264.7 pre-osteoclast cells (BM CM), reduced the proliferation, migration, and invasion of EO771 mammary tumor cells. The same inhibitory effect was obtained with BML284-treated primary human macrophages. In a mouse model, BM CM reduced the progression of mammary tumors and tumor-induced osteolysis and suppressed the tumor invasion to the lung. It also inhibited the differentiation of RANKL-stimulated osteoclasts and enhanced osteoblast differentiation. BM CM was enriched with atypical tumor-suppressing proteins such as Hsp90ab1 and enolase 1 (Eno1). Immunoprecipitation revealed that extracellular Hsp90ab1 interacted with latent TGFβ (LAP-TGFβ) as an inhibitor of TGFβ activation, while Hsp90ab1 and Eno1 interacted and suppressed tumor progression via CD44, a cell-adhesion receptor and a cancer stem cell marker. This study demonstrated that osteoclast-derived CM can be converted into a bone-protective, tumor-suppressing agent by activating Wnt signaling. The results shed a novel insight on the unexplored function of osteoclasts as a potential bone protector that may develop an unconventional strategy to combat bone metastasis.

| S-EPMC8615769 | biostudies-literature

Targeting protective autophagy exacerbates UV-triggered apoptotic cell death.

Project description:Autophagy is activated by various stresses, including DNA damage, and previous studies of DNA damage-induced autophagy have focused on the response to chemotherapeutic drugs, ionizing radiation, and reactive oxygen species. In this study, we investigated the biological significance of autophagic response to ultraviolet (UV) irradiation in A549 and H1299 cells. Our results indicated that UV induces on-rate autophagic flux in these cells. Autophagy inhibition resulting from the knockdown of beclin-1 and Atg5 reduced cell viability and enhanced apoptosis. Moreover, we found that ATR phosphorylation was accompanied by microtubule-associated protein 1 light chain 3B II (LC3B-II) expression during the early phases following UV irradiation, which is a well-established inducer of ATR. Knocking down ATR further attenuated the reduction in LC3B-II at early stages in response to UV treatment. Despite the potential role of ATR in autophagic response, reduced ATR expression does not affect autophagy induction during late phases (24 and 48 h after UV treatment). The result is consistent with the reduced ATR phosphorylation at the same time points and suggests that autophagic response at this stage is activated via a distinct pathway. In conclusion, this study demonstrated that autophagy acts as a cytoprotective mechanism against UV-induced apoptosis and that autophagy induction accompanied with apoptosis at late stages is independent of ATR activation.

| S-EPMC3269747 | biostudies-literature

AFP promotes HCC progression by suppressing the HuR-mediated Fas/FADD apoptotic pathway.

Project description:Hepatocellular carcinoma (HCC) is a major leading cause of cancer-related death worldwide. Alpha fetoprotein (AFP) is reactivated in a majority of hepatocellular carcinoma (HCC) and associated with poor patient outcomes. Although increasing evidence has shown that AFP can regulate HCC cell growth, the precise functions of AFP in hepatocarcinogenesis and the associated underlying mechanism remain incompletely understood. In this study, we demostrated that depleting AFP significantly suppressed diethylnitrosamine (DEN)-induced liver tumor progression in an AFP gene-deficient mouse model. Similarly, knocking down AFP expression inhibited human HCC cell proliferation and tumor growth by inducing apoptosis. AFP expression level was inversely associated with the apoptotic rate in mouse and human HCC specimens. Investigation of potential cross-talk between AFP and apoptotic signaling revealed that AFP exerted its growth-promoting effect by suppressing the Fas/FADD-mediated extrinsic apoptotic pathway. Mechanistically, AFP bound to the RNA-binding protein HuR, increasing the accumulation of HuR in the cytoplasm and subsequent inhibition of Fas mRNA translation. In addition, we found that inhibiting AFP enhanced the cytotoxicity of therapeutics to AFP-positive HCC cells by activating HuR-mediated Fas/FADD apoptotic signaling. Conclusion: Our study defined the pro-oncogenic role of AFP in HCC progression and uncovered a novel antiapoptotic mechanism connecting AFP to HuR-mediated Fas translation. Our findings suggest that AFP is involved in the pathogenesis and chemosensitivity of HCC and that blockade of AFP may be a promising strategy to treat advanced HCC.

| S-EPMC7532541 | biostudies-literature

Synthesis of 2'-formamidonucleoside phosphoramidites for suppressing the seed-based off-target effects of siRNAs

Project description:To investigate effects of siRNA with 2'-formamidonucleoside phosphoramidites (2'-FA) modifications on genome-wide off-target, we analyzed gene expression profile of HeLa cells transfected by their siRNAs. Gene expression profiling

2024-09-30 | GSE274299 | GEO

Characterization of macrophage - cancer cell crosstalk in estrogen receptor positive and triple-negative breast cancer

Project description:We performed whole transcriptome sequencing of human monocytes that were co-cultured with estrogen receptor positive (ER+) or triple-negative (TNBC) breast cancer cell lines and studied the biological responses related to the differential gene activation in both cell types to understand how different cancer cells educate host cells to support tumor growth To characterize the differences in macrophage activation under the influence of either ER+ or TNBC breast cancer cells, we cultured freshly isolated human peripheral monocytes with two breast cancer cell lines (T47D, ER+ and MDA-MB-231, TNBC) in an in vitro transwell co-culture assay. The transwell setting allowed us to investigate the effect of soluble mediators on macrophage activation since direct cell contact of these cells was inhibited by a (PET) membrane (pore size 0.4âÎ¼m).

2015-11-19 | E-GEOD-75130 | biostudies-arrayexpress

Bee Venom Phospholipase A2 Induces Regulatory T Cell Populations by Suppressing Apoptotic Signaling Pathway.

Project description:Bee venom phospholipase A2 is a lipolytic enzyme in bee venom that catalyzes hydrolysis of the sn-2 ester bond of membrane phospholipids to produce free fatty acid and lysophospholipids. Current evidence suggests that bee venom phospholipase A2 (bvPLA2) induces regulatory T cell expansion and attenuates several immune system-related diseases, including Alzheimer's disease. The induction of Treg cells is directly mediated by binding to mannose receptors on dendritic cells. This interaction induces the PGE2-EP2 signaling pathway, which promotes Treg induction in CD4+ T cells. In this study, we investigated the effects of bvPLA2 treatment on the apoptotic signaling pathway in Treg populations. Flow cytometry was performed to identify early apoptotic cells. As a result, early apoptotic cells were dramatically decreased in bvPLA2-treated splenocytes, whereas rapamycin-treated cells showed levels of apoptotic cells similar to those of PBS-treated cells. Furthermore, bvPLA2 treatment increased expression of anti-apoptotic molecules including CTLA-4 and PD-1. The survival rate increased in bvPLA2-treated Tregs. Our findings indicate that bvPLA2-mediated modulation of apoptotic signaling is strongly associated with the Treg induction, which exhibits protective effects against various immune-related diseases. To our knowledge, this study is the first to demonstrate that bvPLA2 is the major bee venom (BV) compound capable of inducing Treg expansion through altering apoptotic signal.

| S-EPMC7150970 | biostudies-literature

The effects of knockdown of PML by different individual siRNAs in HUVEC cells

Project description:To study the potential target genes regulated by PML in endothelial cells, we carried out siRNA-mediated knockdown of PML in HUVEC cells. To eliminate the off-target effects of siRNAs, we utilized two different siRNAs. Only the genes changed in the same pattern following both siRNAs transfection are considered as potential PML-knockdown responsive genes.

2012-05-31 | GSE29238 | GEO

Synthesis of 2'-formamidonucleoside phosphoramidites for suppressing the seed-based off-target effects of siRNAs [RNA-seq]

2024-09-30 | GSE274426 | GEO

The binary toxin CDT enhances Clostridium difficile virulence by suppressing protective colonic eosinophilia.

Project description:Clostridium difficile is the most common hospital acquired pathogen in the USA, and infection is, in many cases, fatal. Toxins A and B are its major virulence factors, but expression of a third toxin, known as C. difficile transferase (CDT), is increasingly common. An adenosine diphosphate (ADP)-ribosyltransferase that causes actin cytoskeletal disruption, CDT is typically produced by the major, hypervirulent strains and has been associated with more severe disease. Here, we show that CDT enhances the virulence of two PCR-ribotype 027 strains in mice. The toxin induces pathogenic host inflammation via a Toll-like receptor 2 (TLR2)-dependent pathway, resulting in the suppression of a protective host eosinophilic response. Finally, we show that restoration of TLR2-deficient eosinophils is sufficient for protection from a strain producing CDT. These findings offer an explanation for the enhanced virulence of CDT-expressing C. difficile and demonstrate a mechanism by which this binary toxin subverts the host immune response.

| S-EPMC5010011 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data