Metformin promotes secretion of mitochondria-rich extracellular vesicles from ADSCs (Met-EVs)
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo Sapiens
SUBMITTER: 
Junnian Zhou
PROVIDER: PXD048824 | iProX | Wed Jan 24 00:00:00 GMT 2024
REPOSITORIES: iProX
Similar Datasets
Project description:Cancer cells consume large amounts of glucose because of their specific metabolic pathway. However, cancer cells exist in tumor tissue where glucose is insufficient. To survive, cancer cells likely have the mechanism to elude their glucose addiction. Here we show that functional mitochondria are essential if cancer cells are to avoid glucose addiction. Cancer cells with dysfunctional mitochondria, such as mitochondrial DNA-deficient rho0 cells and electron transport chain blocker-treated cells, were highly sensitive to glucose deprivation. Our data demonstrated that this sensitization was caused by failure of the unfolded protein response (UPR), an adaptive response mediated by the endoplasmic reticulum (ER). This study suggests a link between mitochondria and the ER during the UPR under glucose deprivation conditions and that mitochondria govern cell fate, not only through ATP production and apoptosis regulation but also through modulating the UPR for cell survival. Human cancer cell lines (HT-1080, HT-29, and mtDNA-deficient cells derived from these cell lines) were selected for RNA extraction and hybridization on Affymetrix microarrays. We examined the unfolded protein response (UPR), an adaptive response mediated by the endoplasmic reticulum (ER), of cancer cells under stress conditions. Abbreviations List: AA, antimycin A; Bu, buformin; Met, metformin; Phen, phenformin; Rot, rotenone; VST, versipelostatin; TM, tunicamycin; 2DG, 2-deoxyglucose; GS, glucose starvation. Capital S (_S) indicates the supernatant of sample including floating cells.
2010-05-28 | E-GEOD-16157 | biostudies-arrayexpress
Project description:Lung cancer is the leading cause of cancer death worldwide and reports innate and acquired therapeutic resistance to cisplatin. Metformin (MET), an antidiabetic agent with potential antitumor activity, overcomes cisplatin resistance in some cancers through AMPK-dependent and independent mechanisms. MET is a potential treatment in cells with LKB1 mutation, even with the impairment of AMPK and overactivation of mTOR signaling. The present study investigated the role of mTOR signaling and other signaling pathways after MET treatment in control and resistant A549 cells, mapping pathways and possible targets for cisplatin sensitivity induced by metformin.
2021-09-09 | PXD017645 | Pride
Project description:To examine the difference of gene expression profiles between malignant melanoma cells treated with neopetasin (NP), metformin (Met), and phenformin (Phen), we have employed microarray expression profiling as a discovery platform. A2058 (human malignant melanoma) cells were treated for 8 hours with NP (3 µM), Met (5,00 µM), and Phen (50 µM).
2021-09-09 | GSE150348 | GEO
Project description:Fanconi anemia (FA) is a disease caused by defective deoxyribonucleic acid (DNA) repair that manifests as bone marrow failure, cancer predisposition, and developmental defects. We previously reported that monotherapy with either metformin (MET) or oxymetholone (OXM) improved peripheral blood (PB) counts and the number and functionality of bone marrow hematopoietic stem progenitor cells (HSPCs) number inFancd2−/−mice. To evaluate whether the combination treatment of these drugs has a synergistic effect to prevent bone marrow failure in FA, we treated cohorts ofFancd2−/−mice and wildtype controls with either MET alone, OXM alone, MET+OXM, or placebo diet from age 3weeks to 18months. The OXM treated animals showed modest improvements in blood parameters including platelet count (p=.01) and hemoglobin levels (p<.05). In addition, the percentage of quiescent hematopoietic stem cell (HSC) (LSK [Lin−Sca+c‐Kit+]) was significantly increased (p=.001) by long‐term treatment with MET alone. The combination of metformin and oxymetholone did not result in a significant synergistic effect in any hematopoietic parameter. Gene expression analysis of liver tissue from these animals showed that some of the expression changes caused byFancd2deletion were partially normalized by metformin treatment. Importantly, no adverse effects of the individual or combination therapies were observed, despite the long‐term administration. We conclude that androgen therapy is not a contraindication to concurrent metformin administration in clinical trials.
2025-05-01 | GSE266448 | GEO
Project description:EVs contain mitochondria that are transferred to condylar DCs. This action triggers ERK1/2/FoxO1/ autophagy pathway internalization of phagocytosed mitochondria by mitochondrial recipient cells, which subsequently affect fatty acid metabolism in DCs to metabolically reprogram them. Thus, DCs changed from an activation state to a tolerance state. Taken together, our findings suggested that EVs reprogram the states of condylar DCs by transferring functional mitochondria into them and affecting their fatty acid metabolism, which highlights the therapeutic value of EVs for TMJOA.
2025-06-04 | GSE265865 | GEO
Project description:Loss of muscle mass and strength following disuse followed by impaired muscle recovery likely contribute to sarcopenia in older adults. Metformin and leucine individually have shown positive effects in skeletal muscle during atrophy conditions but have not been evaluated in combination nor under the conditions of disuse atrophy and recovery in aging. The purpose of this study was to determine if a dual treatment of metformin and leucine (MET+LEU) would prevent disuse-induced atrophy and/or promote muscle recovery in aged mice (22-24 mo). We were also interested if these muscle responses correspond to changes in satellite cells and ECM abundance. Aged mice were subjected to 14 days of hindlimb unloading (HU) followed by 7 or 14 days of reloading (7 or 14d RL). Metformin (MET), leucine (LEU), or MET+LEU was administered via drinking water and were compared to Vehicle-treated mice. We observed that MET+LEU increased whole body grip strength, muscle specific force and satellite cell abundance during HU but did not alter muscle size during HU or RL. Moreover, MET+LEU treatment increased ECM turnover driven by a decrease in collagen IV content during 7 and 14d RL. Transcriptome analysis revealed that MET+LEU altered Gene Set Enrichment Analysis hallmark pathways related to inflammation and myogenesis during HU. Together , MET+LEU was able to improve muscle quality during disuse and recovery in aging possibly by increasing muscle satellite cell content and reducing excessive ECM accumulation.
2021-09-01 | GSE167462 | GEO
Project description:The genome-wide transcriptional response of S. cerevisiae cells upon transfer to carbon-limited or carbon-limited and metformin supplemented media is investigated. DHO strain (BY4742 background) was cultivated batch-wise in SDC media at 30C and 180 rpm up to mid-exponential phase (OD600 ~ 0.6). The cells of the main culture were divided in three aliquots at the mid-exponential phase, centrifuged at 6000 rpm for 5 min, washed twice with deionized and distilled sterile water prior to their transfer to the treatment media. Treatment media comprised of SDC + 0.25% glucose for the C-lim control case and SDC +0.25%glucose + 1.66% metformin for the Met case. Control data for the reference condition (glucose limitation) is derived from E-MTAB-3001. Sample collection for transcriptional profiling was done at the 2nd hour of the transfer. The experiments were carried out in biological triplicates.
2019-07-21 | E-MTAB-6847 | biostudies-arrayexpress
Project description:We have previously demonstrated that the inhibitory effect of metformin on skeletal muscle complex-I linked mitochondrial respiration was associated with attenuated improvements in whole-body insulin sensitivity and cardiorespiratory fitness after aerobic exercise training (AET) in older adults. However, the mechanism(s) by which metformin impacts skeletal muscle adaptations to aerobic exercise remains unclear. To understand potential mechanisms associated with the inhibitory effect of metformin on mitochondrial adaptations to AET, we evaluated the skeletal muscle transcriptome, mitochondrial respiration, and hydrogen peroxide (H2O2) emissions in 7-month-old male C57BL6/J mice after 8-weeks of non-exercise sedentary control (SED) or progressive AET with and without metformin treatment. Metformin attenuated the number of differentially expressed genes by AET (975 vs. 449). Pathway analysis suggests that metformin suppressed several signal transduction pathways involved in oxidative capacity and cellular metabolism, including VEGF, AMPK, HIF-1α, and PI3K-AKT. Notably, the addition of metformin to AET suppressed 16 downstream targets of HIF-1α and was accompanied by metformin ameliorating the increase in mitochondrial respiratory capacity and ADP sensitivity after AET. However, neither AET nor AET+MET impacted mitochondrial H2O2 emitting potential. Given the central role of HIF-1α as an upstream transcriptional regulator of mitochondrial function and biogenesis, these results suggest that suppression of HIF-1α pathway by metformin could serve as a transcriptional regulatory node associated with the inhibitory role of metformin on skeletal muscle mitochondrial adaptations to aerobic exercise training.
2025-03-03 | GSE287490 | GEO
Project description:Metformin is the therapy of choice for treating type 2 diabetes and is currently repurposed for a wide range of diseases including aging. Recent evidence implicates the gut microbiota as a site of metformin action. Combining two tractable genetic models, the bacterium E. coli and the nematode C. elegans, we performed C. elegans RNAseq to investigate the role of the metformin sensitive OP50 and metformin resistant OP50-MR E. coli microbiota in the drug effects on the host. Our data suggest an evolutionarily conserved bacterial mediation of metformin effects on host lipid metabolism and lifespan.
2019-07-13 | E-MTAB-7272 | biostudies-arrayexpress
Project description:Identification of transcriptional profile of several genes involved in diabetes in islet-derived extracellular vesicles (Evs). Recently, EVs are identified as a new mechanism in cell-to-cell communication by transfer of protein and genic information (mRNA, microRNA). Their role is under investigation in immunology, stem cell and cancer, but not in islets and diabetes. The aim of this experiment is to identify mRNA transcripts (in particular, mRNA transcripts involved in diabetes pathophysiology) present in islet Evs.
2012-08-02 | E-MEXP-3695 | biostudies-arrayexpress