Metabolic remodeling of cardiomyocytes identified in phosphoinositide-dependent kinase 1-deficient mice.
Biochem J
; 476(13): 1943-1954, 2019 07 09.
Article
en En
| MEDLINE
| ID: mdl-31208986
ABSTRACT
Metabolic remodeling plays an essential role in the pathophysiology of heart failure (HF). Many studies have shown that the disruption of phosphoinositide-dependent protein kinase-1 (PDK1) caused severe and lethal HF; however, the metabolic pattern of PDK1 deletion remains ambiguous. 1H nuclear magnetic resonance-based metabolomics was applied to explore the altered metabolic pattern in Pdk1-deficient mice. Principle component analysis showed significant separation as early as 4 weeks of age, and dysfunction of metabolism precedes a morphological change in Pdk1-deficient mice. A time trajectory plot indicated that disturbed metabolic patterns were related to the pathological process of the HF in Pdk1-deficient mice, rather than the age of mice. Metabolic profiles demonstrated significantly increased levels of acetate, glutamate, glutamine, and O-phosphocholine in Pdk1 deletion mice. Levels of lactate, alanine, glycine, taurine, choline, fumarate, IMP, AMP, and ATP were significantly decreased compared with controls. Furthermore, PDK1 knockdown decreased the oxygen consumption rate in H9C2 cells as determined using a Seahorse XF96 Analyzer. These findings imply that the disruption of metabolism and impaired mitochondrial activity might be involved in the pathogenesis of HF with PDK1 deletion.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Consumo de Oxígeno
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Miocitos Cardíacos
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Proteínas Quinasas Dependientes de 3-Fosfoinosítido
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Piruvato Deshidrogenasa Quinasa Acetil-Transferidora
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Insuficiencia Cardíaca
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Mitocondrias Cardíacas
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Año:
2019
Tipo del documento:
Article