The Effect of Hypoxia on PGC-1α

Abstract

Markers for mitochondrial function in the skeletal muscle appear to be reduced after extended exposure to altitude. However, short term training at altitude enhances aerobic capacity. Further investigation is needed to determine the skeletal muscle response to altitude. PURPOSE: The purpose of this study was to determine the impact of exposure to normobaric hypoxia after exercise on the gene expression and subcellular location of PGC-1α protein compared to a normoxic environment. METHODS: Six male participants (age 25 ± 2, height 180 ± 4 cm, weight 82 ± 2 kg) completed two 90 min cycling trials in laboratory conditions followed by a 6 h recovery in either ambient conditions (975 m) or in a hypoxic environment (5000 m). Biopsies were taken from the vastus lateralis before exercise, after exercise, and following 6 h recovery. Samples were analyzed for PGC1-α gene expression using RT-qPCR and subcellular location using western blot on cytosolic and nuclear fractions. RESULTS: Exposure to hypoxia following exercise resulted in significantly lower expression of PGC-1α (p = 0.014) but no significant differences were found in protein translocation between the cytosolic (p = 0.225) and nuclear (p = 0.211) fractions. CONCLUSIONS: It appears that the post-translational events of PGC-1α are not altered by acute hypoxia after exercise, despite a reduced transcriptional response of PGC-1α.It is unclear if these cellular events would account for the deficit in mitochondrial function observed with extended exposure to a hypoxic environment. This project was funded by grants from the Department of Defense (W8IXWH-10-Z-0120) and NASA Nebraska Space Grant.