Muscle immobilization and remobilization downregulates PGC-1α signaling and the mitochondrial biogenesis pathway

2013 ◽  
Vol 115 (11) ◽  
pp. 1618-1625 ◽  
Author(s):  
Chounghun Kang ◽  
Li Li Ji
Keyword(s):  
Oxidative Stress ◽  
Cytochrome C ◽  
Muscle Atrophy ◽  
Mitochondrial Biogenesis ◽  
Skeletal Muscle Atrophy ◽  
Control Group ◽  
Ros Generation ◽  
Peroxisome Proliferator ◽  
Protein Loss ◽  
Peroxisome Proliferator Activated Receptor

Prolonged immobilization (IM) results in skeletal muscle atrophy accompanied by increased reactive oxygen species (ROS) generation, inflammation, and protein degradation. However, the biological consequence of remobilizing such muscle has been studied only sparsely. In this study, we examined the peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α)-controlled mitochondrial biogenesis pathway and inflammatory response in mice subjected to 2 wk of hindlimb IM followed by 5 days of remobilization (RM). We hypothesized that ROS generation and activation of redox-sensitive signaling pathways play important roles in the etiology of muscle injury. FVB/N mice (age 2 mo) were randomly assigned to either 14 days of IM by casting one of the hindlimbs ( n = 7), IM followed by 5 days of RM with casting removed ( n = 7), or to a control group (Con; n = 7). Muscle to body weight ratios of three major leg muscles were significantly decreased as a result of IM. Two ubiquitin-proteasome pathway enzymes, muscle atrophy F-box (MAFb or atrogin-1) and muscle ring finger-1 (MuRF-1), were upregulated with IM and maintained at high levels during RM. Protein contents of PGC-1α and nuclear respiratory factors 1 and 2 in tibialis anterior (TA) muscle were reduced by 50% ( P < 0.01) in IM vs. Con, with no recovery observed during RM. IM suppressed mitochondrial transcription factor A and cytochrome- c content by 57% and 63% ( P < 0.01), respectively, and cytochrome- c oxidase activity by 58% ( P < 0.05). Furthermore, mitochondrial DNA content was reduced by 71% ( P < 0.01) with IM. None of these changes were reversed after RM. With RM, TA muscle showed a 2.3-fold ( P < 0.05) higher H2O2 content and a 4-fold ( P < 0.01) higher 8-isoprostane content compared with Con, indicating oxidative stress. Tumor necrosis factor-α and interleukin-6 levels in TA muscle were 4- and 3-fold higher ( P < 0.05), respectively, in IM and RM vs. CON. The nuclear factor-κB (NF-κB) pathway activation was observed only after RM, but not after IM alone. These data indicate an increase in ROS generation during the initial phase of muscle RM that could activate the NF-κB pathway, and elicit inflammation and oxidative stress. These events may hinder muscle recovery from IM-induced mitochondrial deterioration and protein loss.

scholarly journals Antioxidant Apigenin Relieves Age-Related Muscle Atrophy by Inhibiting Oxidative Stress and Hyperactive Mitophagy and Apoptosis in Skeletal Muscle of Mice

2020 ◽  
Vol 75 (11) ◽  
pp. 2081-2088
Author(s):  
Dongtao Wang ◽  
Yajun Yang ◽  
Xiaohu Zou ◽  
Jing Zhang ◽  
Zena Zheng ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Skeletal Muscle ◽  
Muscle Atrophy ◽  
Frailty Index ◽  
Skeletal Muscle Atrophy ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Interacting Protein ◽  
Aged Mice ◽  
Age Related

Abstract Skeletal muscle atrophy in the aged causes loss in muscle mass and functions. Naturally occurring antioxidant flavonoid apigenin is able to ameliorate obesity- and denervation-induced muscle atrophies, but its effects on age-related muscle atrophy remain unknown. We hypothesized that apigenin can relieve muscle atrophy in aged mice, probably through special effects on reactive oxygen species and enzymes with antioxidant functions. For the male mice of the study, apigenin showed significant dose-dependent effects in relieving aging-related muscle atrophy according to results of frailty index as indicator of frailty associated with aging, grip strength, and running distance. Apigenin also improved myofiber size and morphological features and increased mitochondria number and volume, as manifested by succinate dehydrogenase staining and transmission electron microscopy. Our tests also suggested that apigenin promoted activities of enzymes such as superoxide dismutase and glutathione peroxidase for antioxidation and those for aerobic respiration such as mitochondrial respiratory enzyme complexes I, II, and IV, increased ATP, and enhanced expression of genes such as peroxisome proliferator-activated receptor-γ coactivator 1α, mitochondrial transcription factor A, nuclear respiratory factor-1, and ATP5B involved in mitochondrial biogenesis. The data also suggested that apigenin inhibited Bcl-2/adenovirus E1B 19kD-interacting protein 3 and DNA fragmentation as indicators of mitophagy and apoptosis in aged mice with skeletal muscle atrophy. Together, the results suggest that apigenin relieves age-related skeletal muscle atrophy through reducing oxidative stress and inhibiting hyperactive autophagy and apoptosis.

scholarly journals High expressions of the cytoglobin and PGC-1α genes during the tissue regeneration of house gecko (Hemidactylus platyurus) tails

2020 ◽  
Author(s):  
Titta Novianti ◽  
Vetnizah Juniantito ◽  
Ahmad Aulia Jusuf ◽  
Evy Ayu Arida ◽  
Mohamad Sadikin ◽  
...  
Keyword(s):  
Wound Healing ◽  
Tissue Regeneration ◽  
Mitochondrial Biogenesis ◽  
Energy Production ◽  
Energy Levels ◽  
Regeneration Process ◽  
Control Group ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Healing Phase

Abstract Background The tissue regeneration process requires high oxygen and energy levels. Cytoglobin (Cygb) is a member of the globin family, which has the ability to bind oxygen, plays a role in dealing with oxidative stress, and carries oxygen into the mitochondria. Energy production for tissue regeneration is associated with mitochondria—especially mitochondrial biogenesis. The peroxisome proliferator-activated receptor-gamma coactivator (PGC)-1alpha protein helps to regulate mitochondrial biogenesis. House geckos ( Hemidactylus platyurus ) are reptiles that have the ability to regenerate the tissue in their tails. House geckos were selected as the animal models for this study in order to analyze the association of Cygb with oxygen supply and the association of PGC-1α with energy production for tissue regeneration. Results The growth of house gecko tails showed a slow growth at the wound healing phase, then followed by a fast growth after wound healing phase of the regeneration process. While Cygb mRNA expression reached its peak at the wound healing phase and slowly decreased until the end of the observation. PGC-1α mRNA was expressed and reached its peak earlier than Cygb. Conclusions The expressions of both the Cygb and PGC-1α genes were relatively high compared to the control group. We therefore suggest that Cygb and PGC-1α play an important role during the tissue regeneration process. Keywords: cytoglobin, PGC-1α, mitochondrial biogenesis, house gecko, tissue regeneration

scholarly journals Toxicity of Pioglitazone on Mitochondria Isolated from Brain and Heart: An Analysis for Probable Drug-Induced Neurotoxicity and Cardiotoxicity

Drug Research ◽  
2020 ◽  
Vol 70 (02/03) ◽  
pp. 112-118 ◽  
Author(s):  
Enaytollah Seydi ◽  
Tina Servati ◽  
Fatemeh Samiei ◽  
Parvaneh Naserzadeh ◽  
Jalal Pourahmad
Keyword(s):  
Cytochrome C ◽  
Mitochondrial Membrane ◽  
Mitochondrial Swelling ◽  
Ros Generation ◽  
Diabetic Patients ◽  
Peroxisome Proliferator ◽  
Cytochrome C Release ◽  
Drug Induced ◽  
Peroxisome Proliferator Activated Receptor ◽  
Underlying Mechanisms

AbstractPioglitazone (PG) is one of the thiazolidinedione (TZDs) drugs used in diabetic patients. TZDs are known as peroxisome proliferator-activated receptor gamma (PPARγ) agonists. Mitochondria are considered as one of the targets of these drugs. The mechanisms of the effect of PG on mitochondria are not well understood. In this study, we investigated the effect of PG on mitochondria isolated from brain and heart. Mitochondrial parameters such as succinate dehydrogenase (SDH) activity, reactive oxygen species (ROS) generation, collapse in mitochondrial membrane potential (MMP), mitochondrial swelling and cytochrome c release were evaluated. The results showed that PG at concentrations of 12.5, 25 and 50 µg/ml increased the generation of ROS, the collapse of MMP, mitochondrial swelling and the release of cytochrome c in mitochondria isolated from both brain and heart tissues. The underlying mechanisms of PG induced neuro-toxicity and cardio-toxicity may be associated with changes in mitochondrial function, ROS generation (oxidative stress), and changes in the mitochondrial membrane.

Combination of Peroxisome Proliferator-Activated Receptor Gamma (PPARγ) Agonist and PPAR Gamma Co-Activator 1α (PGC-1α) Activator Ameliorates Cognitive Deficits, Oxidative Stress, and Inflammation in Rodent Model of Parkinson's Disease

2021 ◽  
Vol 19 ◽  
Author(s):  
Nihar Ranjan Das ◽  
Bhupesh Vaidya ◽  
Pragyanshu Khare ◽  
Mahendra Bishnoi ◽  
Shyam Sunder Sharma
Keyword(s):  
Oxidative Stress ◽  
Parkinson’S Disease ◽  
Lipoic Acid ◽  
Mitochondrial Biogenesis ◽  
Cognitive Deficits ◽  
Ppar Gamma ◽  
Peroxisome Proliferator ◽  
Alpha Lipoic Acid ◽  
Peroxisome Proliferator Activated Receptor ◽  
Pparγ Agonist

Background: PPAR gamma co-activator 1α (PGC-1α) is known as the master regulator of mitochondrial biogenesis. It is also a co-activator of peroxisome proliferator-activated receptor-gamma (PPARγ) and plays a role in preventing mitochondrial dysfunction in several neurodegenerative disorders, including Parkinson’s disease (PD). Depletion in the levels of these proteins has been linked to oxidative stress, inflammation, and DNA damage, all of which are known to contribute to the pathogenesis of PD. Objective: In the present study, combination therapy of PPARγ agonist (GW1929) and PGC-1α activator (alpha-lipoic acid) was employed to ameliorate cognitive deficits, oxidative stress, and inflammation associated with the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of PD. Results: Our study showed that MPTP-induced PD rats exhibited an increase in oxidative stress and inflammation, leading to cognitive deficits. Furthermore, MPTP-induced PD rats also exhibited reduced mitochondrial biogenesis in comparison to control and sham animals. Intraperitoneal administration of GW 1929 and alpha-lipoic acid in doses lower than those earlier reported individually in literature led to an improvement in the cognitive deficits in comparison to MPTP-induced PD rats. These improvements were accompanied by a reduction in the levels of oxidative stress and inflammation. In addition, an increase in mitochondrial biogenesis was also observed after the combination of these pharmacological agents. Conclusion: Our results provide a rationale for the development of agents targeting PPARγ and PGC-1α as potent therapeutics for the treatment of neurological diseases like PD.

scholarly journals Rhein Relieves Oxidative Stress in an Aβ1-42 Oligomer-Burdened Neuron Model by Activating the SIRT1/PGC-1α-Regulated Mitochondrial Biogenesis

2021 ◽  
Vol 12 ◽  
Author(s):  
Zhihui Yin ◽  
Xinyue Geng ◽  
Zhengyi Zhang ◽  
Ying Wang ◽  
Xiaoyan Gao
Keyword(s):  
Oxidative Stress ◽  
Mitochondrial Biogenesis ◽  
Antioxidant Defense System ◽  
Sirtuin 1 ◽  
Early Event ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Mitochondrial Oxidative Stress ◽  
Nuclear Respiratory Factor ◽  
Nuclear Respiratory Factor 1

Neuronal mitochondrial oxidative stress induced by β-amyloid (Aβ) is an early event of Alzheimer’s disease (AD). Emerging evidence has shown that antioxidant therapy represents a promising therapeutic strategy for the treatment of AD. In this study, we investigated the antioxidant activity of rhein against Aβ1-42 oligomer-induced mitochondrial oxidative stress in primary neurons and proposed a potential antioxidant pathway involved. The results suggested that rhein significantly reduced reactive oxygen species (ROS) level, reversed the depletion of mitochondrial membrane potential, and protected neurons from oxidative stress-associated apoptosis. Moreover, further study indicated that rhein activated mitochondrial biogenesis accompanied by increased cytochrome C oxidase (CytOx) and superoxide dismutase (SOD) activities. CytOx on the respiratory chain inhibited the production of ROS from electron leakage and SOD helped to eliminate excess ROS. Finally, western blot analysis confirmed that rhein remarkedly increased the protein expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) together with its upstream deacetylase sirtuin 1 (SIRT1), and activated downstream transcription factor nuclear respiratory factor 1, promoting mitochondrial biogenesis. In conclusion, our results demonstrate that rhein activates mitochondrial biogenesis regulated by the SIRT1/PGC-1α pathway as an antioxidant defense system against Aβ1-42 oligomer-induced oxidative stress. These findings broaden our knowledge of improving mitochondrial biogenesis as an approach for relieving neuronal oxidative stress in AD.

scholarly journals Heat-Killed Bifidobacterium breve B-3 Enhances Muscle Functions: Possible Involvement of Increases in Muscle Mass and Mitochondrial Biogenesis

Nutrients ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 219
Author(s):  
Kazuya Toda ◽  
Yuki Yamauchi ◽  
Azusa Tanaka ◽  
Tetsuya Kuhara ◽  
Toshitaka Odamaki ◽  
...  
Keyword(s):  
Muscle Mass ◽  
Mitochondrial Biogenesis ◽  
Muscle Metabolism ◽  
Control Group ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Bifidobacterium Breve ◽  
Metabolic Functions ◽  
Group B ◽  
Amp Activated Protein Kinase

A previous clinical study on pre-obesity subjects revealed that Bifidobacterium breve B-3 shows anti-obesity effects and possibly increases muscle mass. Here, we investigated the effects of B-3 on muscle function, such as muscle strength and metabolism, and some signaling pathways in skeletal muscle. Male rodents were orally administered live B-3 (B-3L) or heat-killed B-3 (B-3HK) for 4 weeks. We found that administration of B-3 to rats tended to increase muscle mass and affect muscle metabolism, with stronger effects in the B-3HK group than in the B-3L group. B-3HK significantly increased muscle mass and activated Akt in the rat soleus. With regard to muscle metabolism, B-3HK significantly increased phosphorylated AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptor gamma coactivator (PGC)-1α and cytochrome c oxidase (CCO) gene expression in the rat soleus, suggesting an effect on the AMPK-PGC1α-mitochondrial biogenesis pathway. Furthermore, B-3HK promoted oxidative muscle fiber composition in the gastrocnemius. We also observed a significantly higher level of murine grip strength in the B-3HK group than in the control group. These findings suggest the potential of heat-killed B-3 in promoting muscle hypertrophy and modifying metabolic functions, possibly through the Akt and AMPK pathways, respectively.

scholarly journals Dietary Supplementation With Montmorency Tart Cherries and Exercise Improves Lean Mass in Older C57BL/6 Mice

2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 45-45
Author(s):  
Kara Robinson ◽  
Bethany Hatter ◽  
Karley Washburn ◽  
James Bothwell ◽  
Kendall Anderson ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Body Weight ◽  
Muscle Mass ◽  
Mitochondrial Biogenesis ◽  
Lean Mass ◽  
Treadmill Running ◽  
Peroxisome Proliferator ◽  
Research Committee ◽  
Peroxisome Proliferator Activated Receptor ◽  
Young Mice

Abstract Objectives Sarcopenia, the progressive loss of muscle mass and strength, accelerates with age. Current recommendations to prevent sarcopenia focus on exercise and protein intake. Tart cherry (TC) has shown beneficial effects on muscle recovery following exercise. In this study, we investigated the effects of TC alone and in combination with exercise on lean mass, mitochondrial biogenesis, and oxidative stress in young compared to older mice. Methods In two cohorts (6 & 52 wk-old), female C57BL/6 mice were randomly assigned to 4 groups in a 2 × 2 factorial design with diet (AIN-93 control or TC supplemented at 10% w/w) and exercise as factors. Exercise consisted of treadmill running for 30 min, 5 d/wk, at 12 m/min and a 5° incline. Food intake was recorded daily and body weights weekly. After 8 wks, body composition was assessed using dual-energy x-ray absorptiometry. The gastrocnemius muscle was collected for protein analysis. Western blotting techniques were used to probe for superoxide dismutase 2 (SOD2) and peroxisome proliferator-activated receptor-gamma coactivator 1-alpha (PGC1a), indicators of oxidative stress and mitochondrial biogenesis. Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) was used as loading control. Data were analyzed using 2-way ANOVA with α = 0.05. Results In young mice, TC had no effect on body weight and % lean mass, but led to decreased (P &lt; 0.05) % fat mass compared to controls. Exercise decreased (P &lt; 0.05) body weight and % fat, and tended to increase (P = 0.069) % lean mass. In contrast, TC and exercise independently decreased body weight and % fat, and increased % lean mass in older mice compared to controls. The combination of TC and exercise tended to have a synergistic effect on % lean mass (P = 0.056). Preliminary results show that TC significantly up-regulated SOD2 protein expression in young mice, but no effect was observed with exercise or combined treatments. PGC1α expression tended to be suppressed (P = 0.064) in young animals fed TC. To date, we have been unable to detect changes in SOD2 and PGC1α in older mice. Conclusions TC had a protective effect on lean tissue in older mice, preliminary analyses revealed no alterations in oxidative stress or mitochondrial biogenesis. Further investigation is warranted to understand the benefits of TC on lean muscle mass in older mice. Funding Sources Cherry Research Committee of the Cherry Marketing Institute

scholarly journals High expressions of the cytoglobin and PGC-1α genes during the tissue regeneration of house gecko (Hemidactylus platyurus) tails

2020 ◽  
Author(s):  
Titta Novianti ◽  
Vetnizah Juniantito ◽  
Ahmad Aulia Jusuf ◽  
Evy Ayu Arida ◽  
Mohamad Sadikin ◽  
...  
Keyword(s):  
Wound Healing ◽  
Tissue Regeneration ◽  
Mitochondrial Biogenesis ◽  
Energy Production ◽  
Energy Levels ◽  
Regeneration Process ◽  
Control Group ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Healing Phase

Abstract Background The tissue regeneration process requires high oxygen and energy levels. Cytoglobin (Cygb) is a member of the globin family, which has the ability to bind oxygen, plays a role in dealing with oxidative stress, and carries oxygen into the mitochondria. Energy production for tissue regeneration is associated with mitochondria—especially mitochondrial biogenesis. The peroxisome proliferator-activated receptor-gamma coactivator (PGC)-1alpha protein helps to regulate mitochondrial biogenesis. House geckos ( Hemidactylus platyurus ) are reptiles that have the ability to regenerate the tissue in their tails. House geckos were selected as the animal models for this study in order to analyze the association of Cygb with oxygen supply and the association of PGC-1α with energy production for tissue regeneration. Results The growth of house gecko tails showed a slow growth at the wound healing phase, then followed by a fast growth after wound healing phase of the regeneration process. While Cygb mRNA expression reached its peak at the wound healing phase and slowly decreased until the end of the observation. PGC-1α mRNA was expressed and reached its peak earlier than Cygb. Conclusions The expressions of both the Cygb and PGC-1α genes were relatively high compared to the control group. We therefore suggest that Cygb and PGC-1α play an important role during the tissue regeneration process.

Abstract 292: Brain Derived Neurotrophic Factor Induced Upregulation Of Peroxisome Proliferator-activated Receptor Gamma Coactivator 1-alpha Signaling Prevents Hearts From Heart Failure Progression Against Pressure Overload

2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Ning Feng ◽  
Guangshuo Zhu ◽  
vidhya Sivakumaran ◽  
Manling Zhang ◽  
Djahida Bedja ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Cardiac Function ◽  
Mitochondrial Biogenesis ◽  
Neurotrophic Factor ◽  
Pressure Overload ◽  
Brain Derived Neurotrophic Factor ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Bdnf Signaling

Background: The heart is under the influence of neurotrophins (NTs) secreted from peripheral sympathetic nerves, including brain derived neurotrophic factor (BDNF). BDNF is indispensible for cardiac development and vascular wall integrity. Yet, whether BDNF signaling plays a role in governing cardiac function in response to stress is unclear. Hypothesis: BDNF signaling contributes to maintain proper cardiac structure/function in pressure overloaded mice. Results: BDNF expression is markedly down-regulated in hearts subjected to transverse aortic constriction (TAC). Cardiac specific over-expression of BDNF (BDNF-TG) or administration of a BDNF-mimetic agonist (LM22A-4) preserved cardiac function against pressure overload. In contrast, cardiac-selective deletion of the BDNF receptor, Tropomyosin related kinase receptor B (TrkB), further exacerbated heart failure. In neurons, BDNF up-regulates Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) that regulates energy metabolism and mitochondrial function/biogenesis. Oxidative stress is a major negative modulator of PGC-1a expression/activity. Exposing neonatal rat ventricular myocytes (NRVMs) to hydrogen peroxide downregulated PGC-1α, and BDNF restored it to normal levels, with a concomitant up-regulation of downstream genes involved in both mitochondrial biogenesis and oxidative stress, resulting in attenuated ROS production and increased mitochondrial biogenesis. Consistent with the cultured myocyte findings, PGC-1α and downstream genes were up-regulated in BDNF-TG mice subjected to TAC, associated with attenuated oxidative stress and improved mitochondrial biogenesis; whereas TrkB-/- mice subjected to TAC displayed further decreased PGC-1α expression with worsened oxidative stress and impaired mitochondrial biogenesis. Conclusion: Our data show that BDNF confers protection against pressure overload via enhanced PGC-1α signaling that in turn prevents oxidative stress and improves mitochondrial biogenesis. Our data suggest BDNF/trkB is a promising new therapeutic avenue to prevent or retard heart failure.

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