Autophagy deficient melanocytes display a senescence associated secretory phenotype that includes oxidized lipid mediators
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE83856 | GEO | 2019/06/29
REPOSITORIES: GEO
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Project description:Autophagy is a mechanism that regulates cellular metabolism and clearance of damaged macromolecules and organelles. Impaired degradation of modified macromolecules contributes to cellular dysfunction and is observed in aged tissue and senescent cells. We have inactivated Atg7, an essential autophagy gene, in murine keratinocytes and have found in an earlier study that this resulted in increased baseline oxidative stress and reduced capacity to degrade crosslinked proteins after oxidative ultraviolet stress. To investigate whether autophagy deficiency would promote cellular aging, we studied, how Atg7 deficient (KO) and Atg7 bearing cells (WT) would respond to stress induced by Paraquat (PQ), an oxidant drug commonly used to induce cellular senescence.
2017-02-14 | GSE84935 | GEO
Project description:Ultraviolet (UV) radiation is a major melanoma risk factor, yet underlying mechanisms remain poorly understood. Here we introduce a mouse model permitting fluorescence-aided melanocyte imaging and isolation following in vivo UV irradiation. We use expression profiling to show that activated neonatal skin melanocytes isolated following a melanomagenic UVB dose bear a distinct, persistent interferon-response signature, including genes associated with immunoevasion. UVB-induced melanocyte activation, characterized by aberrant growth and migration, was abolished by antibody-mediated systemic blockade of interferon-gamma (IFN-gamma), but not type-I interferons. IFN-gamma was produced by macrophages recruited to neonatal skin by UVB-induced chemokine receptor Ccr2 ligands. Admixed recruited skin macrophages enhanced transplanted melanoma growth by inhibiting apoptosis; notably, IFN-gamma blockade abolished macrophage-associated melanoma growth and survival. IFN-gamma-producing macrophages were identified in 70% of human melanomas examined. Our data reveal an unanticipated role for IFN-gamma in promoting melanocytic cell survival/immunoevasion, and suggest IFN-gamma-R signaling represents a novel therapeutic melanoma target. Biologic replicates of UVA- and UVB-treated mouse melanocytes, as well as untreated mouse melanocytes and mouse keratinocytes, were used to define melanocyte expression signatures associated with UV treatment.
2011-01-01 | E-GEOD-25164 | biostudies-arrayexpress
Project description:Autophagy deficiency caused by conditional knockout of Atg7 results in severe hepatitis accompanied by abundant accumulation of p62. p62 stablizes Nrf2 by disrupting the association between Keap1 and Nrf2. To understand the pathogenesis of hepatitis under the autophagy deficiency, we examined gene expression profiles of livers from Atg7-null, Nrf2-null and Atg7-Nrf2 double mutant mice. Eight week old Atg7F/F:Mx1-Cre mice and Atg7F/F:Mx1-Cre:Nrf2-/- together with control mice were injected with pIpC. At 4 weeks after pIpC injection, total RNAs were purified from each mouse liver.
2010-10-14 | E-GEOD-20415 | biostudies-arrayexpress
Project description:Ultraviolet (UV) radiation is a major melanoma risk factor, yet underlying mechanisms remain poorly understood. Here we introduce a mouse model permitting fluorescence-aided melanocyte imaging and isolation following in vivo UV irradiation. We use expression profiling to show that activated neonatal skin melanocytes isolated following a melanomagenic UVB dose bear a distinct, persistent interferon-response signature, including genes associated with immunoevasion. UVB-induced melanocyte activation, characterized by aberrant growth and migration, was abolished by antibody-mediated systemic blockade of interferon-gamma (IFN-gamma), but not type-I interferons. IFN-gamma was produced by macrophages recruited to neonatal skin by UVB-induced chemokine receptor Ccr2 ligands. Admixed recruited skin macrophages enhanced transplanted melanoma growth by inhibiting apoptosis; notably, IFN-gamma blockade abolished macrophage-associated melanoma growth and survival. IFN-gamma-producing macrophages were identified in 70% of human melanomas examined. Our data reveal an unanticipated role for IFN-gamma in promoting melanocytic cell survival/immunoevasion, and suggest IFN-gamma-R signaling represents a novel therapeutic melanoma target.
2011-01-01 | GSE25164 | GEO
Project description:Expression array analysis of mice livers with conditional deletion of autophagy related protein 7 (Atg7). Whole RNA from mice livers of 2 month old control (Atg7 FF), Olig1-CRE:Atg7 FF (conditional deletion in hepatocytes) and Alb-CRE:Atg7 FF (conditional deletion in hepatocytes/cholangiocytes) were analyzed. The results provide insight into the gene expression profile and role of autophagy in hepatocytes or hepatocytes/cholangiocytes in hepatic growth regulation and hepatocarcinogenesis.
2016-12-31 | GSE67676 | GEO
Project description:Target genes of ultraviolet stress response in cutaneous melanocytes, potentially associated with solar induced melanocarcinogenesis, were characterized by cDNA microarray technology. In cultured normal human melanocytes, 198 genes out of »9000 arrayed were found modulated > 1.9 times following artificial ultraviolet (mainly ultraviolet-B) irradiation (100 mJ per cm2).
2007-09-15 | E-GEOD-9016 | biostudies-arrayexpress
Project description:Autophagy deficiency caused by conditional knockout of Atg7 results in severe hepatitis accompanied by abundant accumulation of p62. p62 stablizes Nrf2 by disrupting the association between Keap1 and Nrf2. To understand the pathogenesis of hepatitis under the autophagy deficiency, we examined gene expression profiles of livers from Atg7-null, Nrf2-null and Atg7-Nrf2 double mutant mice.
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Project description:we carried out microarray experiments to undestand how the inhibition of autophagy mediated by Atg7 deletion acts as tumor suppresion mechanism cDNA from duodenum of each genotype were prepared
2015-05-26 | E-GEOD-56337 | biostudies-arrayexpress
Project description:Macroautophagy/autophagy is a catabolic process that targets a wide variety of cellular components including proteins, lipids, damaged organelles, and pathogens. The autophagy protein ATG7 is involved in autophagy initiation by facilitating the lipidation of LC3/GABARAPs at the growing autophagosomal membrane. ATG7 is important for normal cellular homeostasis as well as diseased state such as tumor initiation and progression in various tumors. A short isoform of ATG7, termed ATG7(2) in contrast to the full-length ATG7(1), is unable to perform the characterized ATG7 mediated autophagy lipidation activity. In this study, we found that ATG7(1) and ATG7(2) are not correlated in expression in human tissues. They have different patterns of expression indicating that these isoforms are involved in diverse cellular mechanisms. To address the functional role of the short ATG7(2) isoform, we performed mass spectrometry analysis of the protein interactome of ATG7(1) and ATG7(2). This revealed that whereas ATG7(1) interacts with the autophagy machinery, ATG7(2) interacts with key glycolysis and mitochondrial membrane proteins. Functional experiments showed that ATG7(2) expression mediates a decrease in glycolytic activity, opposite to the effects mediated by ATG7(1) expression. These findings suggest a molecular switch between main catabolic processes through isoform dependent expression of a key autophagy gene.
2024-04-15 | PXD040548 | Pride
Project description:To investigate the role of motor neuron autophagy in ALS, we generated mice in which the critical autophagy gene Atg7 was specifically disrupted in motor neurons (Atg7 cKO). We also bred these mice to the SOD1G93A mouse model of ALS. Then we performed RNA sequencing on lumbar spinal cords from these mice to determine how motor neuron autophagy inhibition altered gene expression.
2017-08-10 | GSE100888 | GEO