Dataset Information

Proteomics of Mouse Heart Ventricles Reveals Mitochondria and Metabolism as Major Targets of a Post-Infarction Short-Acting GLP1Ra-Therapy Proteomics of Mouse Heart Ventricles Reveals Mitochondria and Metabolism as Major Targets of a Post-Infarction Short-Acting GLP1Ra-Therapy

ABSTRACT: Cardiovascular disease is the main cause of death worldwide, making it crucial to search for new therapies to mitigate major adverse cardiac events (MACEs) after a cardiac ischemic episode. Drugs in the class of the glucagon-like peptide-1 receptor agonists (GLP1Ra) have demonstrated benefits for heart function and reduced the incidence of MACE in patients with diabetes. Previously, we demonstrated that a short-acting GLP1Ra known as DMB (2-quinoxalinamine, 6,7-dichloro-N-[1,1-dimethylethyl]-3-[methylsulfonyl]-,6,7-dichloro-2-methylsulfonyl-3-N-tert-butylaminoquinoxaline or compound 2, Sigma) also mitigates adverse postinfarction left ventricular remodeling and cardiac dysfunction in lean mice through activation of parkin-mediated mitophagy following infarction. Here, we combined proteomics with in silico analysis to characterize the range of effects of DMB in vivo throughout the course of early postinfarction remodeling. We demonstrate that the mitochondrion is a key target of DMB and mitochondrial respiration, oxidative phosphorylation and metabolic processes such as glycolysis and fatty acid beta-oxidation are the main biological processes being regulated by this compound in the heart. Moreover, the overexpression of proteins with hub properties identified by protein–protein interaction networks, such as Atp2a2, may also be important to the mechanism of action of DMB.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Heart

SUBMITTER: Vidya Venkatraman

LAB HEAD: Dr. Jennifer Van Eyk

PROVIDER: PXD027867 | Pride | 2021-09-07

REPOSITORIES: Pride

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Publications

Proteomics of Mouse Heart Ventricles Reveals Mitochondria and Metabolism as Major Targets of a Post-Infarction Short-Acting GLP1Ra-Therapy.

de Freitas Germano Juliana J Sharma Ankush A Stastna Miroslava M Huang Chengqun C Aniag Marianne M Aceves Angie A Van Eyk Jennifer E JE Mentzer Robert M RM Piplani Honit H Andres Allen M AM Gottlieb Roberta A RA

International journal of molecular sciences 20210813 16

Cardiovascular disease is the main cause of death worldwide, making it crucial to search for new therapies to mitigate major adverse cardiac events (MACEs) after a cardiac ischemic episode. Drugs in the class of the glucagon-like peptide-1 receptor agonists (GLP1Ra) have demonstrated benefits for heart function and reduced the incidence of MACE in patients with diabetes. Previously, we demonstrated that a short-acting GLP1Ra known as DMB (2-quinoxalinamine, 6,7-dichloro-N-[1,1-dimethylethyl]-3-[ ...[more]

PMID: 34445425

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Project description:The pollution of the environment with microplastics has been recognized as an emerging threat worldwide. Due to an exponential increase in production of plastic over the last eight decades and its longevity in the environment, accumulating amounts of microplastic are polluting rivers, lakes and the ocean. Their entry pathways are diverse and still only incompletely understood. Since microplastics are usually defined smaller than 5 mm, it can be ingested by a wide range of aquatic organisms including teleost fish. There are different approaches to study the detrimental effects of pollutants on aquatic organisms. On the one hand, generic baseline parameters such as growth and mortality are regularly considered, often accompanied by established stress parameters such as cortisol, heat shock proteins or lipid oxidation. The conflicting findings to date suggest that these parameters might not be sensitive enough to indicate the physiological effects of environmentally relevant microplastic concentrations. For this reason, more sophisticated biological approaches could provide new insights into whether and how microplastics harm fish. To date, proteomic approaches have been used only sporadically when investigating the effects of microplastic exposure on aquatic organisms. So far, this approach has not been used to address potential microplastic impacts in fish. In the present study, a proteomic approach was trialed alongside established methods in an investigation of fish experiencing long-term exposure to environmentally relevant concentrations of microplastics. Two groups of rainbow trout (Oncorhynchus mykiss were exposed to microplastic concentrations and sizes currently encountered in wild fish and an increased concentration, expected to occur in the near future. These groups where compared to a control group maintained in MP free conditions. Five fish of each treatment were sampled at three time points (week 1, week 4, week 17). The experiments were performed in triplicates, resulting in 45 samples used in the proteomic analysis.

Dataset Information

Proteomics of Mouse Heart Ventricles Reveals Mitochondria and Metabolism as Major Targets of a Post-Infarction Short-Acting GLP1Ra-Therapy Proteomics of Mouse Heart Ventricles Reveals Mitochondria and Metabolism as Major Targets of a Post-Infarction Short-Acting GLP1Ra-Therapy

Publications

Proteomics of Mouse Heart Ventricles Reveals Mitochondria and Metabolism as Major Targets of a Post-Infarction Short-Acting GLP1Ra-Therapy.

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