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Exercise Redox Signalling
Published in James N. Cobley, Gareth W. Davison, Oxidative Eustress in Exercise Physiology, 2022
Ruy A. Louzada, Jessica Bouviere, Rodrigo S. Fortunato, Denise P. Carvalho
The central player in endurance exercise adaptations is the peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) (Handschin and Spiegelman, 2008, 2011). Exercise is a powerful stimulus that induces PGC-1α mRNA and PGC-1α protein expression in rodents and humans (Egan et al., 2010; Little et al., 2010; Miura et al., 2007; Russell et al., 2003). PGC-1α has emerged as a mechanistic link to a wide range of beneficial effects of exercise in muscle, such as mitochondrial biogenesis, angiogenesis, fatty acid utilization, type switching of fibres (Atherton et al., 2005; Narkar et al., 2008), and antioxidant defence (St-Pierre et al., 2006) (Figure 3.3). Importantly, studies in vitro and in vivo have used antioxidant supplementation and specific inhibitors of ROS production, and the results indicated that PGC-1α activity is influenced by ROS, but it seems to be indirect through the activation of p38 MAPK and NF-κB, as well as Ca2+ signalling by these molecules (Nalbandian et al., 2019; Yan, 2009). As antioxidants can prevent or delay any ROS production during contraction in an unspecified manner, more mechanistic insights about the sources of ROS during exercise derived from genetically modified animal models are currently available and have filled the knowledge gap about how health adaptation to exercise are reliant on ROS-mediated signalling.
Mitochondrial Dysfunction in Huntington Disease
Published in Abhai Kumar, Debasis Bagchi, Antioxidants and Functional Foods for Neurodegenerative Disorders, 2021
Md. Hafiz Uddin, Marufa Rumman, Tasnuva Sarowar
PGC-1α plays a crucial role in mitochondrial biogenesis and is targeted by several drugs and natural compounds such as A769662, KD3010, and resveratrol (Figure 9.2) (Dickey et al. 2006; Dickey and La Spada 2018). Several natural flavonoids, namely, epigallocatechin-gallate, naringin, and quercetin, showed promise in protecting against HD and boosted antioxidant defense systems in preclinical models (Solanki et al. 2015). Mitochondrial fission inhibitor P110 targeting Drp1 has shown efficacy in diverse preclinical modes, including different HD mice and HD rats (Mochly-Rosen, Disatnik, and Qi 2014).
Mitochondrial Dysfunction in Chronic Disease
Published in Peter M. Tiidus, Rebecca E. K. MacPherson, Paul J. LeBlanc, Andrea R. Josse, The Routledge Handbook on Biochemistry of Exercise, 2020
Christopher Newell, Heather Leduc-Pessah, Aneal Khan, Jane Shearer
As the primary coactivator responsible for regulation of mitochondrial biogenesis, peroxisome proliferator-activated receptor-γ coactivator 1-α (PGC-1α) acts by regulating mitochondrial protein translation in response to energy balance fluctuations (23). PGC-1α is responsible for co-activating nuclear respiratory factor 2 (NRF2). Alongside NRF2, PGC-1α can then activate nuclear respiratory factor 1 (NRF1), which activates TFAM, a key activator of mitochondrial transcription within the nucleus (105) and regulator of mtDNA replication (35). Collectively, NRF1, NRF2, and TFAM ultimately enable regulation of nuclear encoded mitochondrial proteins in response to mitochondrial biogenesis, while also promoting mtDNA up-regulation to match increases in mitochondrial mass (53).
The peroxisome proliferator-activated receptor γ coactivator-1 alpha rs8192678 (Gly482Ser) variant and hepatitis B virus clearance
Published in Infectious Diseases, 2023
Karima Abounouh, Ikram-Allah Tanouti, Ahd Ouladlahsen, Mohamed Tahiri, Wafaa Badre, Hind Dehbi, M’hammed Sarih, Soumaya Benjelloun, Pascal Pineau, Sayeh Ezzikouri
To date, the rs8192678 polymorphism of PGC-1α has never been studied in association with HBV infection and clearance. In a genotypic analysis of groups of individuals with CHB and those with spontaneously cleared acute HBV infection groups, we found that individuals carrying the T allele were more likely to achieve spontaneous HBV clearance (OR = 0.51, 95% CI: 0.38–0.67), providing an assessment of the T allele and its protective role against HBV infection. This protective effect of rs8192678 was observed against overnutrition-induced hepatocyte fat deposition in an in vitro study [61] and in vivo against hepatic steatosis [61,62]. A cross-sectional study on Mexican-Mestizo Population found that 482Ser allele was associated with a decrease in apolipoprotein B, triglycerides, and glucose [59]. Based on these results they suggested that 482Ser allele carriers have a much healthier metabolic profile. Another study conducted in the USA showed that lower levels of PGC-1α may lead to lower levels of fat accumulation, glucose and fatty acid oxidation [63].
N-acetylcysteine ameliorates monocrotophos exposure-induced mitochondrial dysfunctions in rat liver
Published in Toxicology Mechanisms and Methods, 2022
Jagjeet Singh, Annu Phogat, Vijay Kumar, Vinay Malik
Oxidative stress and reduced endogenous antioxidant defense observed in mitochondrial dysfunctioning can affect sub-cellular signaling that could alter the vital physiology and biochemistry of cellular organelles. PGC-1α is a prime regulator of mitochondrial functioning and biogenesis (Fernandez-Marcos and Auwerx 2011). Enhanced PGC-1α expressions are known to improve the mitochondrial functions in liver and kidney tissue of rats (Peerapanyasut et al. 2019, 2020; Kobroob et al. 2021). In this study, we observed a decrease in gene expression of PGC-1α in MCP-exposed animals. In contrast, NAC treatment enhanced the expression in co-treated rats. Additionally, as PGC-1α is involved in mitochondrial biogenesis, reduction in its expression is also known to decrease various subunits of mitochondria (Sharma et al. 2013); which is in agreement with findings of this study showing reduced gene expression of complex I and IV subunits of mitochondria in MCP exposed rats and its reversal on NAC supplement in co-treated rats. Combining the findings of this study and documentation from literature, it can be speculated that regulation of PGC-1α expression could be another mechanism for NAC mediated protection against MCP exposure-induced mitochondrial dysfunctions in rat liver.
Therapeutic potential of PGC-1α in age-related macular degeneration (AMD) – the involvement of mitochondrial quality control, autophagy, and antioxidant response
Published in Expert Opinion on Therapeutic Targets, 2021
Juha Hyttinen, Janusz Blasiak, Pasi Tavi, Kai Kaarniranta
It is well known that drugs improving insulin resistance activate PGC-1α via PPAR-γ. The interaction involves the activation of a pathway which in normal physiology is linked to neuroprotective mechanism. These drugs have been considered to treat neuroinflammatory conditions, like Alzheimer’s disease, where the expression of PGC-1α is decreased [99]. Rosiglitazone is a PPARγ agonist which is used as an antidiabetic drug; it also has been reported to increase the nuclear fraction of PGC-1α in a mouse model of kidney fibrosis and exert protective effects against oxidative stress and to decrease EMT-derived fibrosis [100]. It has been proposed that rosiglitazone and troglitazone could have potential as wAMD therapy drugs due to their capacity to ameliorate CNV in rodents [101].