PGC-1α-Derived Peptide Influences Energy in Normal Human Dermal Fibroblasts

Abstract

Mitochondrial energy metabolism declines during aging. PGC-1α is a transcription coactivator that plays a key role in the regulation of energetic metabolism and mitochondrial biogenesis in the cells. The aim of this study was to compare the PPARGC1A gene expression level in normal human dermal fibroblasts (NHDF) derived from young and old donors. A PGC-1α-derived peptide was then synthetized and its ability to affect the PPARGC1A gene expression and mitochondrial function was tested. We assessed changes in PPARGC1A gene expression using quantitative RT-PCR. The effect of the PGC-1α-derived peptide on energy production was determined using an ATP bioluminescent assay kit. We also studied changes in mitochondrial membrane potential using JC-1 fluorescent dye and the level of reactive oxygen species (ROS) using DCFH-DA dye in NHDF cells after UVA/B irradiation alone and in combination with a peptide treatment. The PPARGC1A gene expression decreased in an aged human dermal fibroblast. The PGC-1α-derived peptide was synthetized and increased the PPARGC1A gene expression and ATP levels in cells. Furthermore, the mitochondrial membrane potential in UVA/B irradiated cells treated with the tested PGC-1α-derived peptide was increased compared to irradiated controls. Moreover, the ROS levels in UVA/B irradiated cells treated with the PGC-1α-derived peptide decreased. On the basis of our results, PGC-1α emerges as an interesting target to combat decreasing energetic metabolism in aging skin cells. Indeed, the PGC-1α-derived peptide increasing the PPARGC1A gene expression improved the mitochondrial function and increased energy production in the cells.