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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Dataset's files

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			Action	DRS
	MS_181010_LUMOS_D1_1_Rep1.mzid.gz	Mzid
	MS_181010_LUMOS_D1_1_Rep1.mzid_MS_181010_LUMOS_D1_1_Rep1.mgf	Mzid
	MS_181010_LUMOS_D1_1_Rep1.raw	Raw
	MS_181010_LUMOS_D1_1_Rep2.mzid.gz	Mzid
	MS_181010_LUMOS_D1_1_Rep2.mzid_MS_181010_LUMOS_D1_1_Rep2.mgf	Mzid

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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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