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Genetics of endurance
Published in Adam P. Sharples, James P. Morton, Henning Wackerhage, Molecular Exercise Physiology, 2022
Stephen M. Roth, Henning Wackerhage
Does the DNA sequence of these genes vary in humans and does this explain the variation in human exercise capacity? First, the genome-wide sequencing of exons, termed exomes, in 60,706 individuals revealed that all genes are affected by DNA variants that change the amino acid sequence of the encoded proteins and often result in a knockout of the human gene. Some of these knockouts are even homozygous so that there are knockout humans for some genes (17). For example, when searching for DNA variants for PPARGC1A, the gene that encodes the mitochondrial biogenesis regulator protein PGC-1α, the genome aggregation database browser reveals 385 missense SNPs and 5 loss-of-function SNPs, albeit none of these are homozygous (17, 18). This suggests function-modulating DNA sequence variation in genes whose increased or decreased function increases endurance performance, at least in mice. It is therefore a mystery as to why these genes are not highlighted in human GWAS studies where the investigators searched for SNPs that were associated with endurance markers such as VO2max (19).
PGC-1α-siRNA suppresses inflammation in substantia nigra of PD mice by inhibiting microglia
Published in International Journal of Neuroscience, 2023
Xin Guan, Pengyue Wu, Bing Cao, Xiaoting Liu, Xi Chen, Wenpei Zhang, Yanqiu Zhang, Zhenlong Guan, Yanqin Wang
The peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) is a protein that has been widely recognized in recent years as a nuclear transcriptional coactivator and is encoded by the PPARGC1A gene in humans. The PGC-1Α family is comprised of three members: PGC-1α, PGC-1β, and PGC-1Α related coactivator (PRC), which are widely involved in energy metabolism, skeletal muscle physiology, cardiovascular disease, neurodegenerative diseases, and mental disorders. PGC-1α is also the primary regulator of mitochondrial biogenesis. It plays a pivotal role in mitochondrial biogenesis and metabolic processes, and also plays roles in cellular energy metabolism, ROS resistance, mitochondrial function, and the biogenesis transcription effect [9]. PGC-1α is primarily expressed in tissues with high energy supply requirements and abundant mitochondria, including fat, the heart, liver, and skeletal muscle. Studies have shown that PGC-1α can regulate glial cells through the regulation of mitochondria, and that elevated expression of PGC-1α may reduce the progression or slow down the deterioration of neuroinflammation [10–13].
Effects of psychoactive drugs on cellular bioenergetic pathways
Published in The World Journal of Biological Psychiatry, 2021
Chiara C. Bortolasci, Briana Spolding, Srisaiyini Kidnapillai, Mark F. Richardson, Nina Vasilijevic, Sheree D. Martin, Laura J. Gray, Sean L. McGee, Michael Berk, Ken Walder
We were specifically interested in the effects of the drugs on genes encoding components of the electron transport chain, thereby identifying potential effects on OXPHOS. In NT2-N cells, valproate increased the expression of all OXPHOS genes detected (n = 93 genes) by an average of 4.5 ± 0.8% (p < .001, Figure 1). Valproate also specifically increased the expression of genes encoding proteins in Complex 1 (by 4.6 ± 1.3%, p = .001) and Complex 4 (by 6.7 ± 1.5%, p < .001) of the electron transport chain (Figure 2). It was also notable that valproate robustly increased the expression of PPARGC1A in NT2-N cells (by 49 ± 3%, q = 1.14E-08), and tended to increase the expression of other genes involved in mitochondrial biogenesis (PPARA by 27 ± 9%, p = .039; PPARD by 20 ± 4%, p = .0083; PPARG by 33 ± 9%, p = .030; TFAM by 11 ± 2%, p = .0496, Figure 2).
Chicoric acid does not restore palmitate-induced decrease in irisin levels in PBMCs of newly diagnosed patients with T2D and healthy subjects
Published in Archives of Physiology and Biochemistry, 2022
Zahra Arab Sadeghabadi, Roghayeh Abbasalipourkabir, Roohollah Mohseni, Nasrin Ziamajidi
Further, we analysed the effects of palmitate and CA on PPARGC1A expression. We found that palmitate reduces PPARGC1A mRNA levels in PBMCs of both healthy subjects and patients with T2D. Our data is supported by previous research who reported that palmitate reduces PPARGC1A expression in skeletal muscle cells (Coll et al.2006, Crunkhorn et al.2007). We have previously showed that palmitate decreases SIRT1 gene expression. SIRT1 is a key activator of PGC-1α. SIRT1 activates PGC-1α through deacetylation (Sadeghabadi et al.2019). So it is plausible to think that palmitate ameliorated expression of PPARGC1A mRNA through down regulation of SIRT1.