Liang 2016 J Biol Chem: Difference between revisions
No edit summary |
No edit summary |
||
Line 20: | Line 20: | ||
|pathways=N | |pathways=N | ||
|instruments=Oxygraph-2k | |instruments=Oxygraph-2k | ||
}} | }} |
Revision as of 15:12, 20 December 2017
Liang X, Liu J, Zhou D, Lai L, Xiao L, Liu L, Fu T, Kong Y, Zhou Q, Vega RB, Zhu MS, Kelly DP, Gao X, Gan Z (2016) Exercise inducible lactate dehydrogenase B regulates mitochondrial function in skeletal muscle. J Biol Chem 291:25306-18 |
Liang X, Liu J, Zhou D, Lai L, Xiao L, Liu L, Fu T, Kong Y, Zhou Q, Vega RB, Zhu MS, Kelly DP, Gao X, Gan Z (2016) J Biol Chem
Abstract: Lactate dehydrogenase (LDH) catalyzes the interconversion of pyruvate and lactate, which are critical fuel metabolites of skeletal muscle particularly during exercise. However, the physiological relevance of LDH remains poorly understood. Here we show that Ldhb expression is induced by exercise in human muscle and negatively correlated with changes in intramuscular pH levels, a marker of lactate production, during isometric exercise. We found that the expression of Ldhb is regulated by exercise-induced peroxisome proliferator-activated receptor-g coactivator 1ฮฑ (PGC-1ฮฑ). Ldhb gene promoter reporter studies demonstrated that PGC-1ฮฑ activates Ldhb gene expression through multiple conserved estrogen-related receptor (ERR) and myocyte enhancer factor 2 (MEF2) binding sites. Transgenic mice overexpressing Ldhb in muscle (muscle creatine kinase [MCK]-Ldhb) exhibited increased exercise performance and enhanced oxygen consumption during exercise. MCK-Ldhb muscle was shown to have enhanced mitochondrial enzyme activity and increased mitochondrial gene expression, suggesting an adaptive oxidative muscle transformation. In addition, mitochondrial respiration capacity was increased and lactate production decreased in MCK-Ldhb skeletal myotubes in culture. Together, these results identified a previously unrecognized Ldhb-driven alteration in muscle mitochondrial function and suggested a mechanism for the adaptive metabolic response induced by exercise training.
Copyright ยฉ 2016, The American Society for Biochemistry and Molecular Biology. โข Keywords: Bioenergetics, Exercise, Gene regulation, Mitochondria, Skeletal muscle โข Bioblast editor: Kandolf G โข O2k-Network Lab: CN Nanjing Gan Z
Labels: MiParea: Respiration, Exercise physiology;nutrition;life style
Organism: Mouse
Tissue;cell: Skeletal muscle
Preparation: Permeabilized tissue
Coupling state: LEAK, OXPHOS, ET
Pathway: N
HRR: Oxygraph-2k