bims-misrem Biomed News
on Mitochondria and sarcoplasmic reticulum in muscle mass
Issue of 2020‒04‒05
ten papers selected by
Rafael Antonio Casuso Pérez
University of Granada

  1. Life Sci. 2020 Mar 28. pii: S0024-3205(20)30341-6. [Epub ahead of print] 117593
    Yamanashi K, Kinugawa S, Fukushima A, Kakutani N, Takada S, Obata Y, Nakano I, Yokota T, Kitaura Y, Shimomura Y, Anzai T.
      AIMS: Sarcopenia is characterized by muscle mass and strength loss and reduced physical activity. Branched-chain amino acids (BCAAs) were recently described as an activator of protein synthesis via mammalian target of rapamycin (mTOR) signaling for muscle atrophy. In cardiovascular diseases, excessive activation of the renin-angiotensin system may induce an imbalance of protein synthesis and degradation, and this plays a crucial role in muscle atrophy. We investigated the effects of BCAAs on angiotensin II (Ang II)-induced muscle atrophy in mice.MATERIALS AND METHODS: We administered Ang II (1000 ng/kg/min) or vehicle to 10-12-week-old male C57BL/6J mice via subcutaneous osmotic minipumps for 4 weeks with or without BCAA supplementation (3% BCAA in tap water).
    KEY FINDINGS: The skeletal muscle weight/tibial length and cross-sectional area were smaller in the Ang II mice than the vehicle mice; these changes were induced by an imbalance of protein synthesis and degradation signaling such as Akt/mTOR and MuRF-1/Atrogin-1. Compared to the Ang II mice, the mTOR signaling was significantly activated and Ang II-induced muscle atrophy was ameliorated in the Ang II + BCAA mice, and this attenuated the reduction of exercise capacity. Notably, the decrease of muscle weight/tibial length in the fast-twitch dominant muscles (e.g., the extensor digitorum longus) was significantly ameliorated compared to that in the slow-twitch dominant muscles (e.g., soleus). Histologically, the effect of BCAA was larger in fast-twitch than slow-twitch fibers, which may be related to the difference in BCAA catabolism.
    SIGNIFICANCE: BCAA supplementation could contribute to the prevention of skeletal muscle atrophy induced by Ang II.
    Keywords:  Angiotensin II; BCAA; Muscle atrophy; Muscle fiber type
  2. J Transl Med. 2020 Mar 30. 18(1): 142
    Roklicer R, Lakicevic N, Stajer V, Trivic T, Bianco A, Mani D, Milosevic Z, Maksimovic N, Paoli A, Drid P.
      OBJECTIVE: To observe the effect of rapid weight loss (RWL) methods over 3 days on muscle damage in judokas.METHODS: Eighteen judokas participated in this crossover study, meaning that judo athletes were subjected to exercise-only phase (4 days) and RWL phase (3 days). Subjects were tested for myoglobin, creatine kinase, aldolase, hemoglobin, and hematocrit values on seven consecutive days. These biomarkers served as indicators of acute muscle damage.
    RESULTS: During the exercise-only phase, no significant changes were observed. Myoglobin (Mb) (p < 0.001), creatine kinase (CK) (p < 0.001) and aldolase (ALD) (p < 0.001) significantly increased only during the RWL phase, as well as hemoglobin (Hb) (p < 0.001) and hematocrit (Hct) (p < 0.005) values. It was detected that peak values for muscle damage biomarkers were reached on the sixth day, while Hct and Hb values were the highest on the seventh day of the study.
    CONCLUSION: Our study showed significant muscle damage induced by RWL. The prevalence of RWL use by judokas is high but firm scientific evidence is lacking in the evaluation of the current practice of it. Therefore, further knowledge must be gained to evaluate the effectiveness of RWL on performance and its impact on judokas' wellbeing.
    Keywords:  Aldolase; Combat sports; Creatine kinase; Muscle damage; Myoglobin; Weight reduction
  3. Transl Res. 2020 Mar 10. pii: S1931-5244(20)30038-4. [Epub ahead of print]
    Brown LA, Guzman SD, Brooks SV.
      The age-associated decline in muscle mass has become synonymous with physical frailty among the elderly due to its major contribution in reduced muscle function. Alterations in protein and redox homeostasis along with chronic inflammation, denervation, and hormonal dysregulation are all hallmarks of muscle wasting and lead to clinical sarcopenia in older adults. Reduction in skeletal muscle mass has been observed and reported in the scientific literature for nearly 2 centuries; however, identification and careful examination of molecular mediators of age-related muscle atrophy have only been possible for roughly 3 decades. Here we review molecular targets of recent interest in age-related muscle atrophy and briefly discuss emerging small molecule therapeutic treatments for muscle wasting in sarcopenic susceptible populations.
  4. J Appl Physiol (1985). 2020 Apr 02.
    Bellar A, Welch N, Dasarathy S.
      Reduced exercise capacity and impaired physical performance are observed in nearly all patients with liver cirrhosis. Physical activity and exercise are physiological anabolic stimuli that can reverse dysregulated protein homeostasis or proteostasis and potentially increase muscle mass and contractile function in healthy subjects. Cirrhosis is a state of anabolic resistance and unlike the beneficial responses to exercise reported in physiological states, there are few systematic studies evaluating the response to exercise in cirrhosis. Hyperammonemia is a mediator of the liver-muscle axis with net skeletal muscle ammonia uptake in cirrhosis causing signaling perturbations, mitochondrial dysfunction with decreased ATP content, modifications of contractile proteins and impaired ribosomal function, all of which contribute to anabolic resistance in cirrhosis and have the potential to impair the beneficial responses to exercise. English language publications in peer reviewed journals that specifically evaluated the impact of exercise in cirrhosis were reviewed. Most studies evaluated responses to endurance exercise and readouts included peak or maximum oxygen utilization, grip strength, and functional capacity. Endurance exercise for up to 12 weeks is clinically tolerated in well-compensated cirrhosis. Data on the safety of resistance exercise is conflicting. Nutritional supplements enhance the benefits of exercise in healthy subjects but have not been evaluated in cirrhosis. Whether the beneficial physiological responses with endurance exercise and increase in muscle mass with resistance exercise that occur in healthy subjects also occur in cirrhotics is not known. Specific organ-system responses, changes in body composition, or improved long-term clinical outcomes with exercise in cirrhosis need evaluation.
    Keywords:  Cirrhosis; Exercise; Hyperammonemia; safety; sarcopenia
  5. Cells. 2020 Mar 29. pii: E823. [Epub ahead of print]9(4):
    Trinchese G, Cavaliere G, Cimmino F, Catapano A, Carta G, Pirozzi C, Murru E, Lama A, Meli R, Bergamo P, Banni S, Mollica MP.
      Energy balance, mitochondrial dysfunction, obesity, and insulin resistance are disrupted by metabolic inflexibility while therapeutic interventions are associated with improved glucose/lipid metabolism in skeletal muscle. Conjugated linoleic acid mixture (CLA) exhibited anti-obesity and anti-diabetic effects; however, the modulatory ability of its isomers (cis9, trans11, C9; trans10, cis12, C10) on the metabolic flexibility in skeletal muscle remains to be demonstrated. Metabolic inflexibility was induced in rat by four weeks of feeding with a high-fat diet (HFD). At the end of this period, the beneficial effects of C9 or C10 on body lipid content, energy expenditure, pro-inflammatory cytokines, glucose metabolism, and mitochondrial efficiency were examined. Moreover, oxidative stress markers, fatty acids, palmitoyletanolamide (PEA), and oleyletanolamide (OEA) contents along with peroxisome proliferator-activated receptors-alpha (PPARα), AKT, and adenosine monophosphate-activated protein kinase (AMPK) expression were evaluated in skeletal muscle to investigate the underlying biochemical mechanisms. The presented results indicate that C9 intake reduced mitochondrial efficiency and oxidative stress and increased PEA and OEA levels more efficiently than C10 while the anti-inflammatory activity of C10, and its regulatory efficacy on glucose homeostasis are associated with modulation of the PPARα/AMPK/pAKT signaling pathway. Our results support the idea that the dissimilar efficacy of C9 and C10 against the HFD-induced metabolic inflexibility may be consequential to their ability to activate different molecular pathways.
    Keywords:  CLA; metabolic flexibility; mitochondrial function
  6. Cell Metab. 2020 Mar 20. pii: S1550-4131(20)30120-0. [Epub ahead of print]
    Gӧbel J, Engelhardt E, Pelzer P, Sakthivelu V, Jahn HM, Jevtic M, Folz-Donahue K, Kukat C, Schauss A, Frese CK, Giavalisco P, Ghanem A, Conzelmann KK, Motori E, Bergami M.
      Astrocytes have emerged for playing important roles in brain tissue repair; however, the underlying mechanisms remain poorly understood. We show that acute injury and blood-brain barrier disruption trigger the formation of a prominent mitochondrial-enriched compartment in astrocytic endfeet, which enables vascular remodeling. Integrated imaging approaches revealed that this mitochondrial clustering is part of an adaptive response regulated by fusion dynamics. Astrocyte-specific conditional deletion of Mitofusin 2 (Mfn2) suppressed perivascular mitochondrial clustering and disrupted mitochondria-endoplasmic reticulum (ER) contact sites. Functionally, two-photon imaging experiments showed that these structural changes were mirrored by impaired mitochondrial Ca2+ uptake leading to abnormal cytosolic transients within endfeet in vivo. At the tissue level, a compromised vascular complexity in the lesioned area was restored by boosting mitochondrial-ER perivascular tethering in MFN2-deficient astrocytes. These data unmask a crucial role for mitochondrial dynamics in coordinating astrocytic local domains and have important implications for repairing the injured brain.
    Keywords:  Mitofusin 2; angiogenesis; brain injury; brain repair; calcium imaging; contact sites; metabolism; mitochondrial dynamics; perivascular endfeet; proteomics; synthetic linker
  7. Scand J Med Sci Sports. 2020 Apr 04.
    Hoier B, Olsen K, Hanskov DJA, Jorgensen M, Norup LR, Hellsten Y.
      Angiogenic-, mitochondrial- and related transcriptional proteins were assessed in human skeletal muscle and isolated vascular cells during the early phase of endurance training. Thigh muscle biopsies were obtained in healthy young subjects, after one acute bout (n=9) and after 3, 5, 7 and 14 days (n=9) of cycle ergometer training. Whole muscle homogenates were analyzed for angiogenic, mitochondrial, and regulatory mRNA and protein levels. Angiogenic proteins were determined in muscle derived endothelial cells and pericytes sorted by fluorescence activated cell sorting. Acute exercise induced an increase in whole muscle mRNA of peroxisome proliferator-activated receptor gamma coactivator 1 α (PGC1α) (4.5-fold; P=0.002) and vascular endothelial growth factor (VEGF) (2.4-fold; P=0.001) at 2 h post. After 14 days of training there was an increase in CD31 protein (63%; P=0.010) in whole muscle indicating capillary growth. There was also an increase in muscle VEGF receptor 2 (VEGFR2) (1.5-fold; P=0.013), in OXPHOS proteins (complex I, II, IV, V; 1.4 to 1.9-fold; P < 0.05) after 14 days of training and an increase in estrogen related receptor α (ERRα) protein (1.5- fold; P=0.039) at 14 days compared to 5 days of training. Both endothelial cells and pericytes expressed VEGF and other angiogenic factors at the protein level but with a distinctively lower expression of VEGFR2 and thrombospondin-1 (TSP-1) in pericytes. The findings illustrate that initiation of capillary and mitochondrial adaptations occurs within 14 days of training and suggest that sustained changes in angiogenic proteins including VEGF and TSP-1 are moderate in whole muscle and vascular cells.
    Keywords:  Angiogenesis; PGC1α; VEGF; endothelial cells; exercise; mitochondrial adaptation; pericytes; skeletal muscle
  8. Nat Rev Mol Cell Biol. 2020 Mar 30.
    Sies H, Jones DP.
      'Reactive oxygen species' (ROS) is an umbrella term for an array of derivatives of molecular oxygen that occur as a normal attribute of aerobic life. Elevated formation of the different ROS leads to molecular damage, denoted as 'oxidative distress'. Here we focus on ROS at physiological levels and their central role in redox signalling via different post-translational modifications, denoted as 'oxidative eustress'. Two species, hydrogen peroxide (H2O2) and the superoxide anion radical (O2·-), are key redox signalling agents generated under the control of growth factors and cytokines by more than 40 enzymes, prominently including NADPH oxidases and the mitochondrial electron transport chain. At the low physiological levels in the nanomolar range, H2O2 is the major agent signalling through specific protein targets, which engage in metabolic regulation and stress responses to support cellular adaptation to a changing environment and stress. In addition, several other reactive species are involved in redox signalling, for instance nitric oxide, hydrogen sulfide and oxidized lipids. Recent methodological advances permit the assessment of molecular interactions of specific ROS molecules with specific targets in redox signalling pathways. Accordingly, major advances have occurred in understanding the role of these oxidants in physiology and disease, including the nervous, cardiovascular and immune systems, skeletal muscle and metabolic regulation as well as ageing and cancer. In the past, unspecific elimination of ROS by use of low molecular mass antioxidant compounds was not successful in counteracting disease initiation and progression in clinical trials. However, controlling specific ROS-mediated signalling pathways by selective targeting offers a perspective for a future of more refined redox medicine. This includes enzymatic defence systems such as those controlled by the stress-response transcription factors NRF2 and nuclear factor-κB, the role of trace elements such as selenium, the use of redox drugs and the modulation of environmental factors collectively known as the exposome (for example, nutrition, lifestyle and irradiation).
  9. J Physiol. 2020 Apr 04.
    Christiansen D, Eibye K, Hostrup M, Bangsbo J.
      KEY POINTS: Endurance-type training with blood flow restriction (BFR) increases maximum oxygen uptake (V̇O2max) and exercise endurance of humans. However, the physiological mechanisms behind this phenomenon remain uncertain. Here, we show that BFR-interval training reduces the peripheral resistance to oxygen transport during dynamic, submaximal exercise in recreationally-trained men, mainly by increasing convective oxygen delivery to contracting muscles. Accordingly, BFR-training increased oxygen uptake by, and concomitantly reduced net lactate release from, the contracting muscles during relative-intensity-matched exercise, while invoking a similar increase in diffusional oxygen conductance compared to the training control. Only BFR-training increased resting femoral artery diameter, whereas increases in oxygen transport and uptake were dissociated from changes in the skeletal muscle content of mitochondrial electron-transport proteins. Thus, physically trained men benefit from BFR-interval training by increasing leg convective oxygen transport and reducing lactate release, thereby improving the potential for increasing the percentage of V̇O2max that can be sustained throughout exercise.ABSTRACT: In this study, we investigated the effect of training with blood flow restriction (BFR) on thigh oxygen transport and uptake, and lactate release, during exercise. Ten recreationally-trained men (50 ± 5 mL·kg-1 ·min-1 ) completed six weeks of interval cycling with one leg under BFR (BFR-leg; pressure: ∼180 mmHg) and the other leg without BFR (CON-leg). Before and after the training intervention (INT), thigh oxygen delivery, extraction, uptake, diffusion capacity, and lactate release, were determined during knee-extensor exercise at 25% iPPO (Ex1), followed by exercise to exhaustion at 90% pre-training iPPO (Ex2), by measurement of femoral-artery blood flow and femoral-arterial and -venous blood sampling. A muscle biopsy was obtained from legs before and after INT to determine mitochondrial electron-transport protein content. Femoral-artery diameter was also measured. In BFR-leg, after INT, oxygen delivery and uptake were higher, and net lactate release was lower, during Ex1 (vs. CON-leg; p<0.05), with an 11% larger increase in workload (vs. CON-leg; p<0.05). During Ex2, after INT, oxygen delivery was higher, and oxygen extraction was lower, in BFR-leg than CON-leg (p<0.05), resulting in an unaltered oxygen uptake (vs. CON-leg; p>0.05). In CON-leg, at both intensities, oxygen delivery, extraction, uptake, and lactate release, remained unchanged (p>0.05). Resting femoral artery diameter increased with INT only in BFR-leg (∼4%; p<0.05). Oxygen diffusion capacity was similarly raised in legs (p<0.05). Mitochondrial protein content remained unchanged in legs (p>0.05). Thus, BFR-interval training enhances oxygen utilization by, and lowers lactate release from, submaximally-exercising muscles of recreationally-trained men mainly by increasing leg convective oxygen transport. This article is protected by copyright. All rights reserved.
    Keywords:  OXPHOS; Training; aerobic metabolism; blood flow restriction; lactate; mitochondrial protein; oxygen transport; oxygen uptake
  10. Metabolites. 2020 Apr 01. pii: E138. [Epub ahead of print]10(4):
    Ringseis R, Gessner DK, Beer AM, Albrecht Y, Wen G, Most E, Krüger K, Eder K.
      Recently, administration of nicotinic acid (NA) at a pharmacological dose was found to induce a similar change in the muscle´s contractile and metabolic phenotype as observed in response to endurance exercise. Thus, the hypothesis was tested that combined NA administration and endurance exercise promotes the adaptation of muscle to regular exercise and improves the endurance performance to a greater extent than exercise alone. Thus, 30 adult mice were randomly divided into three groups of 10 mice/group. The control and the exercise (EX) group received an adequate NA diet, while the EX + NA group received a high NA diet. Mice of the EX and the EX + NA group were subjected to a treadmill endurance exercise program five times/week during the experimental period of 42 days. At day 41, endurance performance was greater in the EX + NA group than in the control and the EX group (P < 0.05). Mice of the EX + NA group had a higher type IIA (+60%) and a lower type IIB (-55%) fiber percentage in gastrocnemius (GN) muscle than control mice (P < 0.05), while the type I fiber percentage in GN muscle tended to be increased (+100%) in the EX + NA group compared to the control group (P = 0.051). In the EX + NA group, glycogen concentration (+15%) and mRNA levels of two glycolytic (+70-80%) and two glycogenolytic enzymes (+80-120%) in GN muscle were increased compared to the control group (P < 0.05). In conclusion, feeding a high NA diet induces changes in skeletal muscle fiber composition and improves endurance performance of mice subjected to regular endurance exercise.
    Keywords:  adaptation; endurance; exercise; nicotinic acid; skeletal muscle; unfolded protein response