Role of AMP deaminase in diabetic cardiomyopathy.

Autor: Miura T; Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan. miura@sapmed.ac.jp.; Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Hokkaido University of Science, 15-4-1, Maeda-7, Teine-Ku, Sapporo, 006-8585, Japan. miura@sapmed.ac.jp., Kouzu H; Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan., Tanno M; Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan.; Department of Nursing, Sapporo Medical University School of Health Sciences, Sapporo, Japan., Tatekoshi Y; Department of Pharmacology, Sapporo Medical University School of Medicine, Sapporo, Japan., Kuno A; Department of Pharmacology, Sapporo Medical University School of Medicine, Sapporo, Japan.
Jazyk: angličtina
Zdroj: Molecular and cellular biochemistry [Mol Cell Biochem] 2024 Dec; Vol. 479 (12), pp. 3195-3211. Date of Electronic Publication: 2024 Feb 22.
DOI: 10.1007/s11010-024-04951-z
Abstrakt: Diabetes mellitus is one of the major causes of ischemic and nonischemic heart failure. While hypertension and coronary artery disease are frequent comorbidities in patients with diabetes, cardiac contractile dysfunction and remodeling occur in diabetic patients even without comorbidities, which is referred to as diabetic cardiomyopathy. Investigations in recent decades have demonstrated that the production of reactive oxygen species (ROS), impaired handling of intracellular Ca 2+ , and alterations in energy metabolism are involved in the development of diabetic cardiomyopathy. AMP deaminase (AMPD) directly regulates adenine nucleotide metabolism and energy transfer by adenylate kinase and indirectly modulates xanthine oxidoreductase-mediated pathways and AMP-activated protein kinase-mediated signaling. Upregulation of AMPD in diabetic hearts was first reported more than 30 years ago, and subsequent studies showed similar upregulation in the liver and skeletal muscle. Evidence for the roles of AMPD in diabetes-induced fatty liver, sarcopenia, and heart failure has been accumulating. A series of our recent studies showed that AMPD localizes in the mitochondria-associated endoplasmic reticulum membrane as well as the sarcoplasmic reticulum and cytosol and participates in the regulation of mitochondrial Ca 2+ and suggested that upregulated AMPD contributes to contractile dysfunction in diabetic cardiomyopathy via increased generation of ROS, adenine nucleotide depletion, and impaired mitochondrial respiration. The detrimental effects of AMPD were manifested at times of increased cardiac workload by pressure loading. In this review, we briefly summarize the expression and functions of AMPD in the heart and discuss the roles of AMPD in diabetic cardiomyopathy, mainly focusing on contractile dysfunction caused by this disorder.
(© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
Databáze: MEDLINE
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