Lactate as a Metabolic Signal in Gene Expression

Abstract

PURPOSE: Lactate plays an important role in adaptive response of muscle to exercise. The possible contribution gene transcription in causing lactate-induced adaptive responses remains to be discovered. The goal of this study was to assess genome-wide responses of L6 myocytes to lactate. METHODS: L6 myocytes were cultured in Dulbecco's modified Eagle's Medium (high glucose). Eight days following seeding of the cells they were incubated with media containing 0 mM or 20 mM of sodium lactate. The cells were then harvested 1 hr or 6 hr after incubation with lactate. GeneChip analysis (Rat genome 230A2.0, Affymetrix, Santa Clara, CA) was performed as described by manufacturer. Quantitative real-time RT-PCR was performed to validate the data of GeneChip analysis. RESULTS: Twenty mM lactate significantly increased the expression of 33 genes and decreased the expression of 76 genes at 1 hr, and increased the expression of 673 genes and decreased the expression of only 3 genes at 6 hr. Interestingly, 79 genes involved in metabolism and mitochondria were up-regulated at 6 hr and among them, large numbers of genes are related to mitochondria biogenesis. Furthermore, large numbers of genes which are related to trans crip tional activation, transporter, oxidative stress, apoptosis, cell growth, or Ca2+ and muscle were up-regulated at 6 hr. The inductions of monocarboxylate transporter MCT1 and cytochrome c oxidase genes detected by the GeneChip assay were confirmed by real-time RT-PCR. CONCLUSIONS: The GeneChip analysis suggests that lactate accumulation increases mitochondrial biogenesis in L6 myocytes.