Files and links (1)
Published, Version of Record (VoR)CC BY V4.0, Open
Journal article
Myocardial GRK2 Reduces Fatty Acid Metabolism and beta-Adrenergic Receptor-Mediated Mitochondrial Responses
International journal of molecular sciences, v 23(5), p2777
01 Mar 2022
PMID: 35269919
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
G-protein coupled receptor (GPCR) kinase 2 (GRK2) is upregulated in heart failure (HF) patients and mouse models of cardiac disease. GRK2 is a regulator of beta-adrenergic receptors (beta ARs), a GPCR involved in ionotropic and chronotropic responses. We and others have recently reported GRK2 to be localized in the mitochondria, although its function in the mitochondria and/or metabolism remain not clearly defined. We hypothesized that upregulation of GRK2 reduced mitochondrial respiratory function and responses to beta AR activation. Utilizing isolated mouse primary adult cardiomyocytes (ACMs), we investigated the role of glucose, palmitate, ketone bodies, and BCAAs in mediating cell survival. Our results showed that myocyte upregulation of GRK2 promotes palmitate-induced cell death. Isotopologue labeling and mass spectrometry showed that the upregulation of GRK2 reduces beta-hydroxybutyryl CoA generation. Next, using isoproterenol (ISO), a non-selective beta AR-agonist, we determined mitochondrial function in mouse and human primary ACMs. Upregulation of GRK2 impaired ISO-mediated mitochondrial functional responses, which we propose is important for metabolic adaptations in pathological conditions. Increased cardiac levels of GRK2 reduced fatty acid-specific catabolic pathways and impaired ISO-stimulated mitochondrial function. Our data support the notion that GRK2 participates in bioenergetic remodeling and may be an important avenue for the development of novel pharmacological strategies in HF.
Metrics
Details
- Title
- Myocardial GRK2 Reduces Fatty Acid Metabolism and beta-Adrenergic Receptor-Mediated Mitochondrial Responses
- Creators
- Ruxu Zhai - Drexel UniversityErika L. Varner - Temple UniversityAjay Rao - Temple UniversitySunil Karhadkar - Temple UniversityAntonio Di Carlo - Temple UniversityNathaniel W. Snyder - Temple UniversityPriscila Y. Sato - Drexel University
- Publication Details
- International journal of molecular sciences, v 23(5), p2777
- Publisher
- Mdpi
- Number of pages
- 9
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pharmacology and Physiology; A.J. Drexel Autism Institute
- Web of Science ID
- WOS:000767775600001
- Scopus ID
- 2-s2.0-85125557834
- Other Identifier
- 991019167762504721
UN Sustainable Development Goals (SDGs)
This publication has contributed to the advancement of the following goals:
InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology
- Chemistry, Multidisciplinary