Monoamine oxidase-dependent pro-survival signaling in diabetic hearts is mediated by miRNAs
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PROVIDER: PRJNA863650 | ENA |
REPOSITORIES: ENA
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Project description:Monoamine oxidase-dependent pro-survival signaling in diabetic hearts
| PRJNA866484 | ENA
Project description:Diabetes leads to cardiomyopathy and heart failure, the leading cause of death for diabetic patients. Monoamine oxidase (MAO)-dependent reactive oxygen species (ROS) formation contributes to the development of diabetic cardiomyopathy by inducing mitochondrial and cardiomyocyte dysfunction. Yet, it is unclear whether, in addition to the direct effects exerted by MAO-dependent ROS on mitochondria, MAO activity is able to post-transcriptionally regulate cardiomyocyte function and survival in diabetes. To this aim, we performed gene and miRNA expression profiling in cardiac tissue from a mouse model of type 1 diabetes (T1D) with or without pharmacological MAO inhibition. We found that MAO-dependent ROS generation in T1D hearts leads to profound transcriptomic changes, affecting autophagy and pro-survival pathways activation. MAO activity in T1D hearts affected expression levels of miR-133a-3p, -193a-3p, and -27a-3p that target insulin-like growth factor receptor 1 (Igf1r), growth factor receptor bound protein 10 and inositol polyphosphate 4 phosphatase type 1A, respectively, all components of the Igf1r/PI3K/Akt signaling pathway. Indeed, Akt activation was significantly downregulated in T1D hearts, whereas MAO inhibition restored the activation of this pro-survival pathway. The present study provides an important link between MAO activity, transcriptomic changes, and activation of pro-survival signaling and autophagy in diabetic cardiomyopathy.
2022-09-20 | GSE210036 | GEO
Project description:Diabetes leads to cardiomyopathy and heart failure, the leading cause of death for diabetic patients. Monoamine oxidase (MAO)-dependent reactive oxygen species (ROS) formation contributes to the development of diabetic cardiomyopathy by inducing mitochondrial and cardiomyocyte dysfunction. Yet, it is unclear whether, in addition to the direct effects exerted by MAO-dependent ROS on mitochondria, MAO activity is able to post-transcriptionally regulate cardiomyocyte function and survival in diabetes. To this aim, we performed gene and miRNA expression profiling in cardiac tissue from a mouse model of type 1 diabetes (T1D) with or without pharmacological MAO inhibition. We found that MAO-dependent ROS generation in T1D hearts leads to profound transcriptomic changes, affecting autophagy and pro-survival pathways activation. MAO activity in T1D hearts affected expression levels of miR-133a-3p, -193a-3p, and -27a-3p that target insulin-like growth factor receptor 1 (Igf1r), growth factor receptor bound protein 10 and inositol polyphosphate 4 phosphatase type 1A, respectively, all components of the Igf1r/PI3K/Akt signaling pathway. Indeed, Akt activation was significantly downregulated in T1D hearts, whereas MAO inhibition restored the activation of this pro-survival pathway. The present study provides an important link between MAO activity, transcriptomic changes, and activation of pro-survival signaling and autophagy in diabetic cardiomyopathy.
2022-09-20 | GSE210611 | GEO
Project description:Monoamine oxidase-dependent pro-survival signaling in diabetic hearts [total RNA]
| PRJNA866488 | ENA
Project description:This SuperSeries is composed of the SubSeries listed below.
2022-09-20 | GSE210612 | GEO
Project description:Monoamine oxidase A (MAO-A), a mitochondrial enzyme that degrades monoamines including neurotransmitters, is highly expressed in basal cells of the normal human prostatic epithelium and in poorly differentiated (Gleason grades 4 and 5), aggressive prostate cancer (PCa). Clorgyline, an MAO-A inhibitor, induces secretory differentiation of normal prostate cells. We systematically assessed gene expression changes induced by clorgyline in E-CA cells using high-density oligonucleotide microarrays. Genes differentially expressed in treated and control cells were identified by Significance Analysis of Microarrays. Expression of genes of interest was validated by quantitative real-time polymerase chain reaction. time series design
2010-07-17 | E-GEOD-17167 | biostudies-arrayexpress
Project description:Monoamine oxidase A (MAO-A), a mitochondrial enzyme that degrades monoamines including neurotransmitters, is highly expressed in basal cells of the normal human prostatic epithelium and in poorly differentiated (Gleason grades 4 and 5), aggressive prostate cancer (PCa). Clorgyline, an MAO-A inhibitor, induces secretory differentiation of normal prostate cells. We systematically assessed gene expression changes induced by clorgyline in E-CA cells using high-density oligonucleotide microarrays. Genes differentially expressed in treated and control cells were identified by Significance Analysis of Microarrays. Expression of genes of interest was validated by quantitative real-time polymerase chain reaction.
2010-07-17 | GSE17167 | GEO
Project description:A Neurogenic Signature Involving Monoamine Oxidase-A Controls Human Thermogenic Adipose Tissue Development
| PRJNA823047 | ENA
Project description:Transcriptional analysis of the effect of monoamine oxidase B (MAOB) in human prostate stromal cells (PrSC)
| PRJNA778245 | ENA
Project description:AimsMonoamine oxidases (MAOs) are mitochondrial flavoenzymes responsible for neurotransmitter and biogenic amines catabolism. MAO-A contributes to heart failure progression via enhanced norepinephrine catabolism and oxidative stress. The potential pathogenetic role of the isoenzyme MAO-B in cardiac diseases is currently unknown. Moreover, it is has not been determined yet whether MAO activation can directly affect mitochondrial function.ResultsIn wild type mice, pressure overload induced by transverse aortic constriction (TAC) resulted in enhanced dopamine catabolism, left ventricular (LV) remodeling, and dysfunction. Conversely, mice lacking MAO-B (MAO-B(-/-)) subjected to TAC maintained concentric hypertrophy accompanied by extracellular signal regulated kinase (ERK)1/2 activation, and preserved LV function, both at early (3 weeks) and late stages (9 weeks). Enhanced MAO activation triggered oxidative stress, and dropped mitochondrial membrane potential in the presence of ATP synthase inhibitor oligomycin both in neonatal and adult cardiomyocytes. The MAO-B inhibitor pargyline completely offset this change, suggesting that MAO activation induces a latent mitochondrial dysfunction, causing these organelles to hydrolyze ATP. Moreover, MAO-dependent aldehyde formation due to inhibition of aldehyde dehydrogenase 2 activity also contributed to alter mitochondrial bioenergetics.InnovationOur study unravels a novel role for MAO-B in the pathogenesis of heart failure, showing that both MAO-driven reactive oxygen species production and impaired aldehyde metabolism affect mitochondrial function.ConclusionUnder conditions of chronic hemodynamic stress, enhanced MAO-B activity is a major determinant of cardiac structural and functional disarrangement. Both increased oxidative stress and the accumulation of aldehyde intermediates are likely liable for these adverse morphological and mechanical changes by directly targeting mitochondria.
| S-EPMC3887464 | biostudies-literature