Nifedipine Modulates Renal Lipogenesis via the AMPK-SREBP Transcriptional Pathway.
Int J Mol Sci
; 20(7)2019 Mar 29.
Article
em En
| MEDLINE
| ID: mdl-30934807
ABSTRACT
Lipid accumulation in renal cells has been implicated in the pathogenesis of obesity-related kidney disease, and lipotoxicity in the kidney can be a surrogate marker for renal failure or renal fibrosis. Fatty acid oxidation provides energy to renal tubular cells. Ca2+ is required for mitochondrial ATP production and to decrease reactive oxygen species (ROS). However, how nifedipine (a calcium channel blocker) affects lipogenesis is unknown. We utilized rat NRK52E cells pre-treated with varying concentrations of nifedipine to examine the activity of lipogenesis enzymes and lipotoxicity. A positive control exposed to oleic acid was used for comparison. Nifedipine was found to activate acetyl Coenzyme A (CoA) synthetase, acetyl CoA carboxylase, long chain fatty acyl CoA elongase, ATP-citrate lyase, and 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG CoA) reductase, suggesting elevated production of cholesterol and phospholipids. Nifedipine exposure induced a vast accumulation of cytosolic free fatty acids (FFA) and stimulated the production of reactive oxygen species, upregulated CD36 and KIM-1 (kidney injury molecule-1) expression, inhibited p-AMPK activity, and triggered the expression of SREBP-1/2 and lipin-1, underscoring the potential of nifedipine to induce lipotoxicity with renal damage. To our knowledge, this is the first report demonstrating nifedipine-induced lipid accumulation in the kidney.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Transcrição Gênica
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Nifedipino
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Proteína de Ligação a Elemento Regulador de Esterol 1
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Lipogênese
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Proteínas Quinases Ativadas por AMP
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Rim
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Int J Mol Sci
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Taiwan