Effects of Prolonged Dietary Curcumin Exposure on Skeletal Muscle Biochemical and Functional Responses of Aged Male Rats

Oxidative stress resulting from decreased antioxidant protection and increased reactive oxygen and nitrogen species (RONS) production may contribute to muscle mass loss and dysfunction during aging. Curcumin is a phenolic compound shown to upregulate antioxidant defenses and directly quench RONS in vivo. This study determined the impact of prolonged dietary curcumin exposure on muscle mass and function of aged rats. Thirty-two-month-old male F344xBN rats were provided a diet with or without 0.2% curcumin for 4 months. The groups included: ad libitum control (CON; n = 18); 0.2% curcumin (CUR; n = 18); and pair-fed (PAIR; n = 18) rats. CUR rats showed lower food intake compared to CON, making PAIR a suitable comparison group. CUR rats displayed larger plantaris mass and force production (vs. PAIR). Nuclear fraction levels of nuclear factor erythroid-2 related-factor-2 were greater, and oxidative macromolecule damage was lower in CUR (vs. PAIR). There were no significant differences in measures of antioxidant status between any of the groups. No difference in any measure was observed between CUR and CON rats. Thus, consumption of curcumin coupled with reduced food intake imparted beneficial effects on aged skeletal muscle. The benefit of curcumin on aging skeletal muscle should be explored further.

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UPTAKE AND BINDING IN VIVO OF 3H LABELLED ANDROGEN IN THE RAT EPIDIDYMIS AND DUCTUS DEFERENS

Acta Endocrinologica ◽

10.1530/acta.0.0660745 ◽

1971 ◽

Vol 66 (4) ◽

pp. 745-755 ◽

Cited By ~ 17

Author(s):

Vidar Hansson ◽

Kjell J. Tveter

Keyword(s):

Skeletal Muscle ◽

Male Rats ◽

Supernatant Fraction ◽

Nuclear Fraction ◽

Simultaneous Administration ◽

Ductus Deferens ◽

Selective Uptake ◽

Rat Epididymis ◽

Androgen Binding

ABSTRACT Following the administration of [3H] testosterone and [3H]5α-dihydrotestosterone to adult castrated male rats, a selective uptake of androgen was found in the epididymis and ductus deferens,in contrast to the much lower uptake by skeletal muscle. Simultaneous administration of non-labelled androgen reduced the uptake in the epididymis and ductus deferens by about 60–70 per cent. One day after castration, the uptake in the epididymis was about 54 per cent higher than in the intact animals. The 105 000 × g supernatant fraction of homogenates obtained from both the ductus deferens and the epididymis, contained androphilic macromolecules excluded from Sephadex G-100 gel. The 600 × g crude nuclear fraction of homogenized epididymal tissue contained salt extractable androgen binding macromolecules.

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Aerobic Exercise Training and In Vivo Akt Activation Counteract Cancer Cachexia by Inducing a Hypertrophic Profile through eIF-2α Modulation

Cancers ◽

10.3390/cancers14010028 ◽

2021 ◽

Vol 14 (1) ◽

pp. 28

Author(s):

Marcelo G. Pereira ◽

Vanessa A. Voltarelli ◽

Gabriel C. Tobias ◽

Lara de Souza ◽

Gabriela S. Borges ◽

...

Keyword(s):

Skeletal Muscle ◽

Exercise Training ◽

Aerobic Exercise ◽

Muscle Mass ◽

Skeletal Muscle Mass ◽

Cancer Cachexia ◽

Aerobic Exercise Training ◽

Akt Activation ◽

The Impact

Cancer cachexia is a multifactorial and devastating syndrome characterized by severe skeletal muscle mass loss and dysfunction. As cachexia still has neither a cure nor an effective treatment, better understanding of skeletal muscle plasticity in the context of cancer is of great importance. Although aerobic exercise training (AET) has been shown as an important complementary therapy for chronic diseases and associated comorbidities, the impact of AET on skeletal muscle mass maintenance during cancer progression has not been well documented yet. Here, we show that previous AET induced a protective mechanism against tumor-induced muscle wasting by modulating the Akt/mTORC1 signaling and eukaryotic initiation factors, specifically eIF2-α. Thereafter, it was determined whether the in vivo Akt activation would induce a hypertrophic profile in cachectic muscles. As observed for the first time, Akt-induced hypertrophy was able and sufficient to either prevent or revert cancer cachexia by modulating both Akt/mTORC1 pathway and the eIF-2α activation, and induced a better muscle functionality. These findings provide evidence that skeletal muscle tissue still preserves hypertrophic potential to be stimulated by either AET or gene therapy to counteract cancer cachexia.

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Knockdown of the E3 Ubiquitin ligase UBR5 and its role in skeletal muscle anabolism

10.1101/2020.06.05.116145 ◽

2020 ◽

Cited By ~ 2

Author(s):

Daniel C. Turner ◽

David C. Hughes ◽

Leslie M. Baehr ◽

Robert A. Seaborne ◽

Mark Viggars ◽

...

Keyword(s):

Gene Expression ◽

Skeletal Muscle ◽

Muscle Mass ◽

Ubiquitin Ligase ◽

Muscle Protein ◽

E3 Ubiquitin Ligase ◽

Skeletal Muscle Atrophy ◽

Human Myotubes ◽

The Impact

AbstractUBR5 is an E3-ubiquitin-ligase positively associated with anabolism, hypertrophy and recovery from atrophy in skeletal muscle. The precise mechanisms underpinning UBR5’s role in the regulation of skeletal muscle mass remain unknown. The present study aimed to elucidate these mechanisms by silencing the UBR5 gene in-vitro and in-vivo. The siRNA-induced reduction (−77%) in UBR5 gene expression in human myotubes was prevented by mechanical loading, suggesting that UBR5 gene expression may be regulated via mechano-transduction signalling. Therefore, we electroporated a UBR5-RNAi plasmid into mouse tibialis anterior muscle in-vivo to investigate the impact of reduced UBR5 on mechano-transduction signalling MEK/ERK/p90RSK and Akt/p70S6K/4E-BP1/rpS6 pathways. Seven days post UBR5 RNAi electroporation, while reductions in overall muscle mass were not detected, mean CSA of GFP-positive fibers was reduced (−9.5%) and the number of large fibers was lower versus the control. Importantly, UBR5-RNAi significantly reduced total RNA, muscle protein synthesis, ERK1/2 and Akt phosphorylation. Whilst p90RSK phosphorylation significantly increased, total p90RSK protein levels demonstrated a 45% reduction with UBR5-RNAi. Finally, these early signalling events after 7 days of UBR5 knockdown culminated in significant reductions in muscle mass (−4.6%) and larger reductions in fiber CSA (−18.5%) after 30 days. This was associated with increased levels of the phosphatase, PP2Ac, and inappropriate chronic elevation of p70S6K and rpS6 between 7 and 30 days, and corresponding reductions in eIF4e. This study demonstrates UBR5 plays an important role in anabolism/hypertrophy, whereby knockdown of UBR5 culminates in skeletal muscle atrophy.

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Evaluating the effect of 20-hydroxyecdysone (20HE) on mechanistic target of rapamycin complex 1 (mTORC1) signaling in the skeletal muscle and liver of rats

Applied Physiology Nutrition and Metabolism ◽

10.1139/apnm-2015-0301 ◽

2015 ◽

Vol 40 (12) ◽

pp. 1324-1328 ◽

Cited By ~ 8

Author(s):

Tracy G. Anthony ◽

Emily T. Mirek ◽

Albert Raouf Bargoud ◽

Lindsey Phillipson-Weiner ◽

Christopher M. DeOliveira ◽

...

Keyword(s):

Skeletal Muscle ◽

Protein Kinase ◽

Protein Kinase B ◽

Nutritional Supplements ◽

Male Rats ◽

Target Of Rapamycin ◽

Mechanistic Target Of Rapamycin ◽

Mtorc1 Signaling ◽

The Impact

Phytoecdysteroids such as 20-hydroxyecdysone (20HE) are nutritional supplements marketed as enhancers of lean body mass. In this study the impact of 20HE ingestion on protein kinase B/Akt-mechanistic target of rapamycin complex 1 signaling in the skeletal muscle and liver of male rats was found to be limited. Bioavailability of 20HE, whether consumed alone or with leucine, also remained low at all doses ingested. Additional work is necessary to clarify 20HE mechanism of action in vivo.

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Regulation of glucose transporter GLUT-4 and hexokinase II gene transcription by insulin and epinephrine

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1997.273.4.e682 ◽

1997 ◽

Vol 273 (4) ◽

pp. E682-E687 ◽

Cited By ~ 11

Author(s):

Jared P. Jones ◽

G. Lynis Dohm

Keyword(s):

Skeletal Muscle ◽

Gene Transcription ◽

Glucose Transporter ◽

Male Rats ◽

Rat Skeletal Muscle ◽

Hexokinase Ii ◽

Epinephrine Infusion ◽

Glut 4 ◽

Gastrocnemius Muscles

Transport of glucose across the plasma membrane by GLUT-4 and subsequent phosphorylation of glucose by hexokinase II (HKII) constitute the first two steps of glucose utilization in skeletal muscle. This study was undertaken to determine whether epinephrine and/or insulin regulates in vivo GLUT-4 and HKII gene transcription in rat skeletal muscle. In the first experiment, adrenodemedullated male rats were fasted 24 h and killed in the control condition or after being infused for 1.5 h with epinephrine (30 μg/ml at 1.68 ml/h). In the second experiment, male rats were fasted 24 h and killed after being infused for 2.5 h at 1.68 ml/h with saline or glucose (625 mg/ml) or insulin (39.9 μg/ml) plus glucose (625 mg/ml). Nuclei were isolated from pooled quadriceps, tibialis anterior, and gastrocnemius muscles. Transcriptional run-on analysis indicated that epinephrine infusion decreased GLUT-4 and increased HKII transcription compared with fasted controls. Both glucose and insulin plus glucose infusion induced increases in GLUT-4 and HKII transcription of twofold and three- to fourfold, respectively, compared with saline-infused rats. In conclusion, epinephrine and insulin may regulate GLUT-4 and HKII genes at the level of transcription in rat skeletal muscle.

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In vivo uptake of [14C]leucine by skeletal muscle ribosomes after injury in rats fed two levels of protein

British Journal Of Nutrition ◽

10.1079/bjn19690034 ◽

1969 ◽

Vol 23 (2) ◽

pp. 271-280 ◽

Cited By ~ 6

Author(s):

V. R. Young ◽

P. C. Huang

Keyword(s):

Skeletal Muscle ◽

Specific Activity ◽

Male Rats ◽

Thigh Muscle ◽

Left Femur ◽

The Right ◽

And Control ◽

The Relationship ◽

In Vivo Uptake

1. After 14 days on a diet containing 5 or 25% casein male rats received a fracture of the left femur. Four hours before they were killed the injured and control rats were injected with [1-14C]leucine; the incorporation of radioactivity into an isolated fraction of skeletal muscle ribosomes was studied 6, 12, 24, 48, 72, 96 and 228 h after injury.2. The incorporation of [14C]leucine into the ribosome fraction in right thigh muscles dropped to 40% of control values 72 h after fracture in well-nourished rats and after 96 h with diets containing 5 or 25%, casein.3. The specific activity of the trichloroacetic acid-soluble fraction of muscle from injured rats was equal to or higher than that of the controls during the first 72 h but lower at 96 h.4. These results suggest that a reduced incorporation of amino acids by ribosomes from the right thigh muscle occurred on day 3 after fracture in the group receiving 25% casein but not in the group receiving 5% casein.5. Muscle RNA and DNA concentrations were not affected by the injury.6. The relationship between these findings and the loss of muscle N after injury is discussed.

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Inhibiting myosin-ATPase reveals a dynamic range of mitochondrial respiratory control in skeletal muscle

Biochemical Journal ◽

10.1042/bj20110366 ◽

2011 ◽

Vol 437 (2) ◽

pp. 215-222 ◽

Cited By ~ 93

Author(s):

Christopher G. R. Perry ◽

Daniel A. Kane ◽

Chien-Te Lin ◽

Rachel Kozy ◽

Brook L. Cathey ◽

...

Keyword(s):

Skeletal Muscle ◽

Dynamic Range ◽

Energy Charge ◽

Respiratory Control ◽

Basic Research ◽

Dependent Manner ◽

Atpase Inhibitor ◽

Wide Range ◽

The Impact

Assessment of mitochondrial ADP-stimulated respiratory kinetics in PmFBs (permeabilized fibre bundles) is increasingly used in clinical diagnostic and basic research settings. However, estimates of the Km for ADP vary considerably (~20–300 μM) and tend to overestimate respiration at rest. Noting that PmFBs spontaneously contract during respiration experiments, we systematically determined the impact of contraction, temperature and oxygenation on ADP-stimulated respiratory kinetics. BLEB (blebbistatin), a myosin II ATPase inhibitor, blocked contraction under all conditions and yielded high Km values for ADP of >~250 and ~80 μM in red and white rat PmFBs respectively. In the absence of BLEB, PmFBs contracted and the Km for ADP decreased ~2–10-fold in a temperature-dependent manner. PmFBs were sensitive to hyperoxia (increased Km) in the absence of BLEB (contracted) at 30 °C but not 37 °C. In PmFBs from humans, contraction elicited high sensitivity to ADP (Km<100 μM), whereas blocking contraction (+BLEB) and including a phosphocreatine/creatine ratio of 2:1 to mimic the resting energetic state yielded a Km for ADP of ~1560 μM, consistent with estimates of in vivo resting respiratory rates of <1% maximum. These results demonstrate that the sensitivity of muscle to ADP varies over a wide range in relation to contractile state and cellular energy charge, providing evidence that enzymatic coupling of energy transfer within skeletal muscle becomes more efficient in the working state.

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Knockdown of the E3 ubiquitin ligase UBR5 and its role in skeletal muscle anabolism

AJP Cell Physiology ◽

10.1152/ajpcell.00432.2020 ◽

2021 ◽

Vol 320 (1) ◽

pp. C45-C56

Author(s):

David C. Hughes ◽

Daniel C. Turner ◽

Leslie M. Baehr ◽

Robert A. Seaborne ◽

Mark Viggars ◽

...

Keyword(s):

Skeletal Muscle ◽

Muscle Mass ◽

Ubiquitin Ligase ◽

Fluorescent Protein ◽

Muscle Protein ◽

Muscle Protein Synthesis ◽

Tibialis Anterior Muscle ◽

E3 Ubiquitin Ligase ◽

Skeletal Muscle Atrophy ◽

The Impact

UBR5 is an E3 ubiquitin ligase positively associated with anabolism, hypertrophy, and recovery from atrophy in skeletal muscle. The precise mechanisms underpinning UBR5’s role in the regulation of skeletal muscle mass remain unknown. The present study aimed to elucidate these mechanisms by silencing the UBR5 gene in vivo. To achieve this aim, we electroporated a UBR5-RNAi plasmid into mouse tibialis anterior muscle to investigate the impact of reduced UBR5 on anabolic signaling MEK/ERK/p90RSK and Akt/GSK3β/p70S6K/4E-BP1/rpS6 pathways. Seven days after UBR5 RNAi electroporation, although reductions in overall muscle mass were not detected, the mean cross-sectional area (CSA) of green fluorescent protein (GFP)-positive fibers were reduced (−9.5%) and the number of large fibers were lower versus the control. Importantly, UBR5-RNAi significantly reduced total RNA, muscle protein synthesis, ERK1/2, Akt, and GSK3β activity. Although p90RSK phosphorylation significantly increased, total p90RSK protein levels demonstrated a 45% reduction with UBR5-RNAi. Finally, these early events after 7 days of UBR5 knockdown culminated in significant reductions in muscle mass (−4.6%) and larger reductions in fiber CSA (−18.5%) after 30 days. This was associated with increased levels of phosphatase PP2Ac and inappropriate chronic elevation of p70S6K and rpS6 between 7 and 30 days, as well as corresponding reductions in eIF4e. This study demonstrates that UBR5 plays an important role in anabolism/hypertrophy, whereby knockdown of UBR5 culminates in skeletal muscle atrophy.

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In Vivo Anti-Inflammatory Potential of Viscozyme®-Treated Jujube Fruit

Foods ◽

10.3390/foods9081033 ◽

2020 ◽

Vol 9 (8) ◽

pp. 1033 ◽

Cited By ~ 2

Author(s):

Yoonsu Kim ◽

Jisun Oh ◽

Chan Ho Jang ◽

Ji Sun Lim ◽

Jeong Soon Lee ◽

...

Keyword(s):

Lung Inflammation ◽

Radical Scavenging ◽

Lung Epithelial Cells ◽

Lung Damage ◽

Antioxidant Defenses ◽

Heme Oxygenase 1 ◽

Related Factor ◽

Nuclear Factor ◽

Jujube Fruit

The fruit of Ziziphus jujuba, commonly called jujube, has long been consumed for its health benefits. The aim of this study was to examine the protective effect of dietary supplementation of enzymatically hydrolyzed jujube against lung inflammation in mice. The macerated flesh of jujube was extracted with aqueous ethanol before and after Viscozyme treatment. The extract of enzyme-treated jujube, called herein hydrolyzed jujube extract (HJE), contained higher levels of quercetin, total phenolics, and flavonoids, and exhibited more effective radical-scavenging abilities in comparison to non-hydrolyzed jujube extract (NHJE). HJE treatment decreased production of inflammation-associated molecules, including nitric oxide and pro-inflammatory cytokines from activated Raw 264.7 or differentiated THP-1 cells. HJE treatment also reduced expression of nuclear factor-κB and its downstream proteins in A549 human lung epithelial cells. Moreover, oral supplementation of 1.5 g of HJE per kg of body weight (BW) attenuated histological lung damage, decreased plasma cytokines, and inhibited expression of inflammatory proteins and oxidative stress mediators in the lungs of mice exposed to benzo(a)pyrene at 50 mg/kg BW. Expression levels of antioxidant and cytoprotective factors, such as nuclear factor erythroid-derived 2-related factor 2 and heme oxygenase-1, were increased in lung and liver tissues from mice treated with HJE, compared to mice fed NHJE. These findings indicate that dietary HJE can reduce benzo(a)pyrene-induced lung inflammation by inhibiting cytokine release from macrophages and promoting antioxidant defenses in vivo.

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