期刊
FASEB JOURNAL
卷 21, 期 10, 页码 2602-2612出版社
WILEY
DOI: 10.1096/fj.07-8174com
关键词
muscle; lactate shuttle; lactate oxidation complex; exercise; cell signaling
资金
- NIAMS NIH HHS [R01 AR050459] Funding Source: Medline
We hypothesized that in addition to serving as a fuel source and gluconeogenic precursor, lactate anion (La-) is a signaling molecule. Therefore, we screened genome-wide responses of L6 cells to elevated ( 10 and 20 mM) sodium-La- added to buffered, high-glucose media. Lactate increased reactive oxygen species (ROS) production and up-regulated 673 genes, many known to be responsive to ROS and Ca2+ . The induction of genes encoding for components of the mitochondrial lactate oxidation complex was confirmed by independent methods (PCR and EMSA). Specifically, lactate increased monocarboxylate transporter-1 (MCT1) mRNA and protein expression within 1 h and cytochrome c oxidase ( COX) mRNA and protein expression in 6 h. Increases in COX coincided with increases in peroxisome proliferator activated-receptor gamma coactivator-1 alpha (PGC1 alpha) expression and the DNA binding activity of nuclear respiratory factor (NRF)-2. We conclude that the lactate signaling cascade involves ROS production and converges on transcription factors affecting mitochondrial biogenesis.
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