scholarly journals Thyroid Hormone Stimulation of Autophagy Is Essential for Mitochondrial Biogenesis and Activity in Skeletal Muscle

Endocrinology ◽  
2016 ◽  
Vol 157 (1) ◽  
pp. 23-38 ◽  
Author(s):  
Ronny Lesmana ◽  
Rohit A. Sinha ◽  
Brijesh K. Singh ◽  
Jin Zhou ◽  
Kenji Ohba ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Thyroid Hormone ◽  
Protein Kinase ◽  
Mitochondrial Biogenesis ◽  
Mitochondrial Protein ◽  
Adenosine Monophosphate ◽  
Mitochondrial Activity ◽  
Dependent Manner ◽  
In Vivo Models ◽  
Stimulation Of

Abstract Thyroid hormone (TH) and autophagy share similar functions in regulating skeletal muscle growth, regeneration, and differentiation. Although TH recently has been shown to increase autophagy in liver, the regulation and role of autophagy by this hormone in skeletal muscle is not known. Here, using both in vitro and in vivo models, we demonstrated that TH induces autophagy in a dose- and time-dependent manner in skeletal muscle. TH induction of autophagy involved reactive oxygen species (ROS) stimulation of 5′adenosine monophosphate-activated protein kinase (AMPK)-Mammalian target of rapamycin (mTOR)- Unc-51-like kinase 1 (Ulk1) signaling. TH also increased mRNA and protein expression of key autophagy genes, microtubule-associated protein light chain 3 (LC3), Sequestosome 1 (p62), and Ulk1, as well as genes that modulated autophagy and Forkhead box O (FOXO) 1/3a. TH increased mitochondrial protein synthesis and number as well as basal mitochondrial O2 consumption, ATP turnover, and maximal respiratory capacity. Surprisingly, mitochondrial activity and biogenesis were blunted when autophagy was blocked in muscle cells by Autophagy-related gene (Atg)5 short hairpin RNA (shRNA). Induction of ROS and 5′adenosine monophosphate-activated protein kinase (AMPK) by TH played a significant role in the up-regulation of Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PPARGC1A), the key regulator of mitochondrial synthesis. In summary, our findings showed that TH-mediated autophagy was essential for stimulation of mitochondrial biogenesis and activity in skeletal muscle. Moreover, autophagy and mitochondrial biogenesis were coupled in skeletal muscle via TH induction of mitochondrial activity and ROS generation.

scholarly journals The Trifunctional Protein Mediates Thyroid Hormone Receptor-Dependent Stimulation of Mitochondria Metabolism

2012 ◽  
Vol 26 (7) ◽  
pp. 1117-1128 ◽  
Author(s):  
E. Sandra Chocron ◽  
Naomi L. Sayre ◽  
Deborah Holstein ◽  
Nuttawut Saelim ◽  
Jamal A. Ibdah ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Thyroid Hormone ◽  
Protein Kinase ◽  
Hormone Receptor ◽  
Thyroid Hormone Receptor ◽  
Mitochondrial Metabolism ◽  
Dependent Manner ◽  
Compound C ◽  
Amp Activated Protein Kinase ◽  
Stimulation Of

Abstract We previously demonstrated that the thyroid hormone, T3, acutely stimulates mitochondrial metabolism in a thyroid hormone receptor (TR)-dependent manner. T3 has also recently been shown to stimulate mitochondrial fatty acid oxidation (FAO). Here we report that TR-dependent stimulation of metabolism is mediated by the mitochondrial trifunctional protein (MTP), the enzyme responsible for long-chain FAO. Stimulation of FAO was significant in cells that expressed a nonnuclear amino terminus shortened TR isoform (sTR43) but not in adult fibroblasts cultured from mice deficient in both TRα and TRβ isoforms (TRα−/−β−/−). Mouse embryonic fibroblasts deficient in MTP (MTP−/−) did not support T3-stimulated FAO. Inhibition of fatty-acid trafficking into mitochondria using the AMP-activated protein kinase inhibitor 6-[4-(2-piperidin-1-yl-ethoxy)-phenyl)]-3-pyridin-4-yl-pyrrazolo[1,5-a]-pyrimidine (compound C) or the carnitine palmitoyltransferase 1 inhibitor etomoxir prevented T3-stimulated FAO. However, T3 treatment could increase FAO when AMP-activated protein kinase was maximally activated, indicating an alternate mechanism of T3-stimulated FAO exists, even when trafficking is presumably high. MTPα protein levels and higher molecular weight complexes of MTP subunits were increased by T3 treatment. We suggest that T3-induced increases in mitochondrial metabolism are at least in part mediated by a T3-shortened TR isoform-dependent stabilization of the MTP complex, which appears to lower MTP subunit turnover.

Mechanisms of calcium-induced mitochondrial biogenesis and GLUT4 synthesis

2007 ◽  
Vol 32 (5) ◽  
pp. 840-845 ◽  
Author(s):  
David C. Wright
Keyword(s):  
Skeletal Muscle ◽  
Protein Kinase ◽  
Mitochondrial Biogenesis ◽  
Glucose Transporter ◽  
Mitochondrial Protein ◽  
Mitogen Activated Protein Kinase ◽  
Peroxisome Proliferator ◽  
Adaptive Responses ◽  
Peroxisome Proliferator Activated Receptor ◽  
Skeletal Muscle Insulin Resistance

Regularly performed aerobic exercise leads to increases in skeletal muscle mitochondria and glucose transporter 4 (GLUT4) protein content, resulting in an enhanced capacity to oxidize substrates and improvements in insulin- and contraction-mediated glucose uptake. Although the specific mechanisms governing these adaptive responses have not been fully elucidated, accumulating evidence suggests that the increase in cytosolic Ca2+ that occurs with each wave of sacrolemmal depolarization is a key component of these processes. Treating L6 muscle cells with agents that increase Ca2+ without causing reductions in ~P or the activation of 5′-AMP-activated protein kinase leads to increases in GLUT4 and mitochondrial protein contents. This effect is likely controlled through calcium/calmodulin-dependent protein kinase (CaMK), since KN93, a specific CaMK inhibitor, blocks these adaptive responses. Recent findings provide evidence that the activation of p38 mitogen-activated protein kinase (MAPK) is involved in the pathway through which Ca2+/CaMK mediates mitochondrial and GLUT4 biogenesis. p38 MAPK initiates GLUT4 and mitochondrial biogenesis through the activation      of transcription factors and transcriptional coactivators such as myocyte enhancer factor 2 (MEF2) and peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α). Subsequent increases in the content of these proteins further enhance Ca2+-induced GLUT4 and mitochondrial biogenesis. Since decreases in mitochondrial and GLUT4 contents are associated with skeletal muscle insulin resistance, an understanding of the mechanisms by which these processes can be normalized will aid in the prevention and treatment of type 2 diabetes.

scholarly journals Nanocurcumin potential to increase mitochondrial biogenesis in skeletal muscle via AMPK-PGC-1alpha

2021 ◽  
Author(s):  
Hamidie Ronald D. Ray ◽  
◽  
Asep Bayu Dani Nandiyanto ◽  
Rita Patriasih ◽  
Abdullah Firmansah ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Expression ◽  
Endurance Exercise ◽  
Mitochondrial Biogenesis ◽  
Curcuma Longa ◽  
Mitochondrial Protein ◽  
Natural Antioxidants ◽  
Adenosine Monophosphate ◽  
Exercise Group ◽  
Mitochondrial Markers

Curcumin, which comes from the rhizome Curcuma longa L, is known as the polyphenol with a high level content of natural antioxidants and has benefits on pharmacological activities and human health. The purpose of current study was to investigate the effect of nanocurcumin itself and the combination with exercise on 5' adenosine monophosphate-activated protein kinase (AMPK), PGC-1α, and mitochondrial protein expression of cytochrome c oxidase subunit IV (COX-IV), in rat gastrocnemius muscle. Animals separated to be non-endurance exercise and endurance exercise group. Curcumin and nanocurcumin with doses 100 mg per kg-body weight per day were given peroral in both groups for 28 days in order to determine the effect of nanocurcumin on mitochondrial markers including AMPK-PGC-1α and COX-IV. Western blotting (WB) method was applied to investigate the protein expression on skeletal muscle. The result showed that nanocurcumin increased mitochondrial marker protein COX-IV on non exercise and exercise groups. Furthermore, our result demonstrated that nanocurcumin treatment combined with exercise increased the phosphorylation of AMPK and PGC-1α. Addition, nanocurcumin treatment alone, without exercise, also increased PGC-1α protein expression. This current result suggests that nanocurcumin could increase mitochondrial biogenesis markers. When it is used together with exercise, it potentially has the additive effect of exercise to increase mitochondrial markers through AMPK-PGC-1α signaling pathway. In conclusion, nanocurcumin treatment combined with exercise potentially increases mitochondrial biogenesis.

Polydatin Attenuates Carbachol-induced Contraction of Guinea Pig Gallbladder

2019 ◽  
Vol 18 (1) ◽  
pp. 34-38
Author(s):  
Chen Lei ◽  
Pan Xiang ◽  
Shen Yonggang ◽  
Song Kai ◽  
Zhong Xingguo ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Guinea Pig ◽  
Smooth Muscles ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Cyclic Guanosine Monophosphate ◽  
Guanosine Monophosphate ◽  
Dependent Manner ◽  
Underlying Mechanisms ◽  
Dose Dependent

The aim of this study was to determine whether polydatin, a glucoside of resveratrol isolated from the root of Polygonum cuspidatum, warranted development as a potential therapeutic for ameliorating the pain originating from gallbladder spasm disorders and the underlying mechanisms. Guinea pig gallbladder smooth muscles were treated with polydatin and specific inhibitors to explore the mechanisms underpinning polydatin-induced relaxation of carbachol-precontracted guinea pig gallbladder. Our results shown that polydatin relaxed carbachol-induced contraction in a dose-dependent manner through the nitric oxide/cyclic guanosine monophosphate/protein kinase G and the cyclic adenosine monophosphate/protein kinase A signaling pathways as well as the myosin light chain kinase and potassium channels. Our findings suggested that there was value in further exploring the potential therapeutic use of polydatin in gallbladder spasm disorders.

scholarly journals AMP-Activated Protein Kinase as a Key Trigger for the Disuse-Induced Skeletal Muscle Remodeling

2018 ◽  
Vol 19 (11) ◽  
pp. 3558 ◽  
Author(s):  
Natalia Vilchinskaya ◽  
Igor Krivoi ◽  
Boris Shenkman
Keyword(s):  
Skeletal Muscle ◽  
Protein Kinase ◽  
Histone Deacetylases ◽  
Molecular Mechanisms ◽  
Weight Bearing ◽  
Mammalian Target Of Rapamycin ◽  
Adenosine Monophosphate ◽  
Chain Gene ◽  
Mtorc1 Signaling ◽  
The Impact

Molecular mechanisms that trigger disuse-induced postural muscle atrophy as well as myosin phenotype transformations are poorly studied. This review will summarize the impact of 5′ adenosine monophosphate -activated protein kinase (AMPK) activity on mammalian target of rapamycin complex 1 (mTORC1)-signaling, nuclear-cytoplasmic traffic of class IIa histone deacetylases (HDAC), and myosin heavy chain gene expression in mammalian postural muscles (mainly, soleus muscle) under disuse conditions, i.e., withdrawal of weight-bearing from ankle extensors. Based on the current literature and the authors’ own experimental data, the present review points out that AMPK plays a key role in the regulation of signaling pathways that determine metabolic, structural, and functional alternations in skeletal muscle fibers under disuse.

AMP-activated protein kinase activity and glucose uptake in rat skeletal muscle

2001 ◽  
Vol 280 (5) ◽  
pp. E677-E684 ◽  
Author(s):  
Nicolas Musi ◽  
Tatsuya Hayashi ◽  
Nobuharu Fujii ◽  
Michael F. Hirshman ◽  
Lee A. Witters ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Kinase ◽  
Glucose Uptake ◽  
Muscle Contractions ◽  
Treadmill Running ◽  
Dependent Manner ◽  
Rat Skeletal Muscle ◽  
Amp Activated Protein Kinase ◽  
Dose Dependent

The AMP-activated protein kinase (AMPK) has been hypothesized to mediate contraction and 5-aminoimidazole-4-carboxamide 1-β-d-ribonucleoside (AICAR)-induced increases in glucose uptake in skeletal muscle. The purpose of the current study was to determine whether treadmill exercise and isolated muscle contractions in rat skeletal muscle increase the activity of the AMPKα1 and AMPKα2 catalytic subunits in a dose-dependent manner and to evaluate the effects of the putative AMPK inhibitors adenine 9-β-d-arabinofuranoside (ara-A), 8-bromo-AMP, and iodotubercidin on AMPK activity and 3- O-methyl-d-glucose (3-MG) uptake. There were dose-dependent increases in AMPKα2 activity and 3-MG uptake in rat epitrochlearis muscles with treadmill running exercise but no effect of exercise on AMPKα1 activity. Tetanic contractions of isolated epitrochlearis muscles in vitro significantly increased the activity of both AMPK isoforms in a dose-dependent manner and at a similar rate compared with increases in 3-MG uptake. In isolated muscles, the putative AMPK inhibitors ara-A, 8-bromo-AMP, and iodotubercidin fully inhibited AICAR-stimulated AMPKα2 activity and 3-MG uptake but had little effect on AMPKα1 activity. In contrast, these compounds had absent or minimal effects on contraction-stimulated AMPKα1 and -α2 activity and 3-MG uptake. Although the AMPKα1 and -α2 isoforms are activated during tetanic muscle contractions in vitro, in fast-glycolytic fibers, the activation of AMPKα2-containing complexes may be more important in regulating exercise-mediated skeletal muscle metabolism in vivo. Development of new compounds will be required to study contraction regulation of AMPK by pharmacological inhibition.

scholarly journals Effect of Quercetin Treatment on Mitochondrial Biogenesis and Exercise-Induced AMP-Activated Protein Kinase Activation in Rat Skeletal Muscle

Nutrients ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 729 ◽  
Author(s):  
Keiichi Koshinaka ◽  
Asuka Honda ◽  
Hiroyuki Masuda ◽  
Akiko Sato
Keyword(s):  
Skeletal Muscle ◽  
Protein Kinase ◽  
Endurance Exercise ◽  
Mitochondrial Biogenesis ◽  
Exercise Performance ◽  
Term Therapy ◽  
High Dose ◽  
Rat Skeletal Muscle ◽  
Amp Activated Protein Kinase ◽  
Quercetin Treatment

The purpose of this study was to evaluate the effect of chronic quercetin treatment on mitochondrial biogenesis, endurance exercise performance and activation levels of AMP-activated protein kinase (AMPK) in rat skeletal muscle. Rats were assigned to a control or quercetin group and were fed for 7 days. Rats treated with quercetin showed no changes in the protein levels of citrate synthase or cytochrome C oxidase IV or those of sirtuin 1, peroxisome proliferator-activated receptor gamma coactivator-1α or phosphorylated AMPK. After endurance swimming exercise, quercetin-treated rats demonstrated no differences in blood and muscle lactate levels or glycogen utilization speed compared to control rats. These results indicate that quercetin treatment does not stimulate mitochondrial biogenesis in skeletal muscle and does not influence metabolism in a way that might enhance endurance exercise capacity. On the other hand, the AMPK phosphorylation level immediately after exercise was significantly lower in quercetin-treated muscles, suggesting that quercetin treatment might provide a disadvantage to muscle adaptation when administered with exercise training. The molecular results of this study indicate that quercetin treatment may not be advantageous for improving endurance exercise performance, at least after high-dose and short-term therapy.

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