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- Title
Nifedipine Modulates Renal Lipogenesis via the AMPK-SREBP Transcriptional Pathway.
- Authors
Peng, Chiung-Chi; Lin, Yen-Chung; Wu, Mai-Szu; Lin, Yuh-Feng; Chen, Kuan-Chou; Chen, Chang-Rong; Chen, Chang-Yu; Chen, Chang-Jui; Shen, Che-Chou
- 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.
- Subjects
NIFEDIPINE; CALCIUM antagonists; ADENOSINE monophosphate; STEROLS; LIPID synthesis
- Publication
International Journal of Molecular Sciences, 2019, Vol 20, Issue 7, p1570
- ISSN
1661-6596
- Publication type
Article
- DOI
10.3390/ijms20071570