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Hypoxia muscle atrophy

Yong-Soo Lee, Ja-Yeon Kim, Kyung-Soo Oh, Seok Won Chung
BACKGROUND: Fatty infiltration in skeletal muscle is directly linked to loss of muscle strength and is associated with various adverse physical outcomes such as muscle atrophy, inflammation, insulin resistance, mobility impairments, and even mortality in the elderly. Aging, mechanical unloading, muscle injury, and hormonal imbalance are main causes of muscle fat accumulation, and the fat cells are derived from muscle stem cells via adipogenic differentiation. However, the pathogenesis and molecular mechanisms of fatty infiltration in muscles are still not fully defined...
April 5, 2017: Journal of Cachexia, Sarcopenia and Muscle
N R W Martin, K Aguilar-Agon, G P Robinson, D J Player, M C Turner, S D Myers, M P Lewis
Contemporary tissue engineered skeletal muscle models display a high degree of physiological accuracy compared with native tissue, and therefore may be excellent platforms to understand how various pathologies affect skeletal muscle. Chronic obstructive pulmonary disease (COPD) is a lung disease which causes tissue hypoxia and is characterised by muscle fibre atrophy and impaired muscle function. In the present study we exposed engineered skeletal muscle to varying levels of oxygen (O2 ; 21-1%) for 24 hours in order to see if a COPD like muscle phenotype could be recreated in vitro, and if so, at what degree of hypoxia this occured...
March 10, 2017: Journal of Cellular Biochemistry
J P Gumucio, M D Flood, A Bedi, H F Kramer, A J Russell, C L Mendias
OBJECTIVES: Rotator cuff tears are among the most frequent upper extremity injuries. Current treatment strategies do not address the poor quality of the muscle and tendon following chronic rotator cuff tears. Hypoxia-inducible factor-1 alpha (HIF-1α) is a transcription factor that activates many genes that are important in skeletal muscle regeneration. HIF-1α is inhibited under normal physiological conditions by the HIF prolyl 4-hydroxylases (PHDs). In this study, we used a pharmacological PHD inhibitor, GSK1120360A, to enhance the activity of HIF-1α following the repair of a chronic cuff tear, and measured muscle fibre contractility, fibrosis, gene expression, and enthesis mechanics...
January 2017: Bone & Joint Research
Franciele Przygodda, Leandro Henrique Manfredi, Juliano Machado, Dawit A P Gonçalves, Neusa Maria Zanon, Leni G H Bonagamba, Benedito H Machado, Isis do Carmo Kettelhut, Luiz C C Navegantes
Although it is well known that chronic hypoxia induces muscle wasting, the effects of intermit-tent hypoxia on skeletal muscle protein metabolism remains unclear. We hypothesized that acute intermittent hypoxia (AIH), a challenge that activates the hypothalamic-pituitary-adrenal axis, would alter muscle protein homeostasis through a glucocorticoid-dependent mechanism. Three-week-old rats were submitted to adrenalectomy (ADX) and exposed to 8 h of AIH (6% O2 for 40s at 9 min intervals). Animals were sacrificed and the soleus and extensor digitorum longus (EDL) muscles were harvested and incubated in vitro for measurements of protein turn-over...
December 8, 2016: Journal of Applied Physiology
Gommaar D'Hulst, Alessandra Ferri, Damien Naslain, Luc Bertrand, Sandrine Horman, Marc Francaux, David J Bishop, Louise Deldicque
Chronic hypoxia leads to muscle atrophy. The molecular mechanisms responsible for this phenomenon are not well defined in vivo. We sought to determine how chronic hypoxia regulates molecular markers of protein synthesis and degradation in human skeletal muscle and whether these regulations were related to the regulation of the hypoxia-inducible factor (HIF) pathway. Eight young male subjects lived in a normobaric hypoxic hotel (FiO2 14.1%, 3,200 m) for 15 days in well-controlled conditions for nutrition and physical activity...
2016: Hypoxia
Shantanu Dixit, Chaithra Kalkur, Atul P Sattur, Michael M Bornstein, Fred Melton
BACKGROUND: Scleroderma is a chronic connective tissue disorder with unknown etiology. It is characterized by excessive deposition of extracellular matrix in the connective tissues causing vascular disturbances which can result in tissue hypoxia. These changes are manifested as atrophy of the skin and/or mucosa, subcutaneous tissue, muscles, and internal organs. Such changes can be classified into two types, namely, morphea (localized) and diffuse (systemic). Morphea can manifest itself as hemifacial atrophy (Parry-Romberg syndrome) although this remains debatable...
October 24, 2016: Journal of Medical Case Reports
Gommaar D'Hulst, Louise Deldicque
Skeletal muscle wasting has been shown to be a mechanism by which humans are able to adapt to extreme altitude. Nonetheless, the literature is conflicting regarding the altitude or time point at which this phenomenon starts to occur. Using the metric recently suggested by Garvivan-Lewis et al. (8), we propose an hypoxic dose of 5000 km·h as the cut-off point above which hypoxia-induced muscle atrophy starts to develop. As such, we suggest that both elevation and hours of altitude exposure should be incorporated in future studies unraveling hypoxic regulation of muscle mass...
October 14, 2016: Journal of Applied Physiology
Teng Ma, Lei Zhu, Yafeng Yang, Xin Quan, Liangliang Huang, Zhongyang Liu, Zhen Sun, Shu Zhu, Jinghui Huang, Zhuojing Luo
Local hypoxia in the early stages of peripheral nerve injury is a challenge for axonal regeneration. To address this issue, perfluorotributylamine (PFTBA)-based oxygen carrying fibrin hydrogel was prepared and injected into Schwann cell (SC)-seeded collagen-chitosan conduits to increase oxygen supply to SCs within the conduits. The conduit containing PFTBA-SC gel was then applied to bridge a 15-mm sciatic nerve defect in rats. It was observed that most of the GFP-labeled SCs initially seeded in the PFTBA hydrogel remained alive for approximately 28 days after their in vivo implantation...
September 4, 2016: Journal of Tissue Engineering and Regenerative Medicine
Corinna Preuße, Yves Allenbach, Olaf Hoffmann, Hans-Hilmar Goebel, Debora Pehl, Josefine Radke, Alexandra Doeser, Udo Schneider, Rieke H E Alten, Tilmann Kallinich, Olivier Benveniste, Arpad von Moers, Benedikt Schoser, Ulrike Schara, Werner Stenzel
Dermatomyositis (DM) can occur in both adults and juveniles with considerable clinical differences. The links between immune-mediated mechanisms and vasculopathy with respect to development of perifascicular pathology are incompletely understood. We investigated skeletal muscle from newly diagnosed, treatment-naïve juvenile (jDM) and adult dermatomyositis (aDM) patients focusing on hypoxia-related pathomechanisms, vessel pathology, and immune mechanisms especially in the perifascicular region. Therefore, we assessed the skeletal muscle biopsies from 21 aDM, and 15 jDM patients by immunohistochemistry and electron microscopy...
2016: Acta Neuropathologica Communications
Tanja Taivassalo, Sabah N A Hussain
COPD is a significant public health challenge, notably set to become the third leading cause of death and fifth leading cause of chronic disability worldwide by the next decade. Skeletal muscle impairment is now recognized as a disabling, extrapulmonary consequence of COPD that is associated with reduced quality of life and premature mortality. Because COPD typically manifests in older individuals, these clinical features may overlie normal age-associated declines in muscle function and performance. Although physical inactivity, oxidative stress, inflammation, hypoxia, malnutrition, and medications all likely contribute to this comorbidity, a better understanding of the underlying mechanism is needed to develop effective therapies...
May 2016: Chest
Philip Lewis, David Sheehan, Renata Soares, Ana Varela Coelho, Ken D O'Halloran
Mechanisms underpinning chronic sustained hypoxia (CH)-induced structural and functional adaptations in respiratory muscles are unclear despite the clinical relevance to respiratory diseases. The objectives of the present study were to thoroughly assess the putative role of CH-induced redox remodeling in murine diaphragm muscle over time and the subsequent effects on metabolic enzyme activities, catabolic signaling and catabolic processes, and diaphragm muscle contractile function. C57Bl6/J mice were exposed to normoxia or normobaric CH (fraction of inspired oxygen = 0...
July 2016: American Journal of Respiratory Cell and Molecular Biology
Roxana Rodríguez-Romo, Kenia Benítez, Jonatan Barrera-Chimal, Rosalba Pérez-Villalva, Arturo Gómez, Diana Aguilar-León, Jesús F Rangel-Santiago, Sara Huerta, Gerardo Gamba, Norma Uribe, Norma A Bobadilla
Despite clinical recovery of patients from an episode of acute kidney injury (AKI), progression to chronic kidney disease (CKD) is possible on long-term follow-up. However, mechanisms of this are poorly understood. Here, we determine whether activation of angiotensin-II type 1 receptors during AKI triggers maladaptive mechanisms that lead to CKD. Nine months after AKI, male Wistar rats develop CKD characterized by renal dysfunction, proteinuria, renal hypertrophy, glomerulosclerosis, tubular atrophy, and tubulointerstitial fibrosis...
February 2016: Kidney International
Eilidh Somers, Robert D Lees, Katie Hoban, James N Sleigh, Haiyan Zhou, Francesco Muntoni, Kevin Talbot, Thomas H Gillingwater, Simon H Parson
OBJECTIVE: Spinal muscular atrophy (SMA) is a major inherited cause of infant death worldwide. It results from mutations in a single, ubiquitously expressed gene (SMN1), with loss of lower motor neurons being the primary pathological signature. Systemic defects have also been reported in SMA patients and animal models. We investigated whether defects associated with the vasculature contribute to motor neuron pathology in SMA. METHODS: Development and integrity of the capillary bed was examined in skeletal muscle and spinal cord of SMA mice, and muscle biopsies from SMA patients and controls, using quantitative morphometric approaches on immunohistochemically labeled tissue...
February 2016: Annals of Neurology
Xiangwei Liu, Xiaolei Sun, Hua Liao, Zhen Dong, Jingjing Zhao, Hong Zhu, Peng Wang, Li Shen, Lei Xu, Xin Ma, Cheng Shen, Fan Fan, Cong Wang, Kai Hu, Yunzeng Zou, Junbo Ge, Jun Ren, Aijun Sun
OBJECTIVE: Revascularization is an essential process to compensate for cardiac underperfusion and, therefore, preserves cardiac function in the face of chronic ischemic injury. Recent evidence suggested a vital role of aldehyde dehydrogenase 2 (ALDH2) in cardiac protection after ischemia. This study was designed to determine whether ALDH2 regulates chronic ischemia-induced angiogenesis and to explore the underlying mechanism involved. Moreover, the clinical impact of the ALDH2 mutant allele on the development of coronary collateral circulation (CCC) was evaluated...
October 2015: Arteriosclerosis, Thrombosis, and Vascular Biology
F B Favier, F A Britto, D G Freyssenet, X A Bigard, H Benoit
Skeletal muscle is a metabolically active tissue and the major body protein reservoir. Drop in ambient oxygen pressure likely results in a decrease in muscle cells oxygenation, reactive oxygen species (ROS) overproduction and stabilization of the oxygen-sensitive hypoxia-inducible factor (HIF)-1α. However, skeletal muscle seems to be quite resistant to hypoxia compared to other organs, probably because it is accustomed to hypoxic episodes during physical exercise. Few studies have observed HIF-1α accumulation in skeletal muscle during ambient hypoxia probably because of its transient stabilization...
December 2015: Cellular and Molecular Life Sciences: CMLS
Christian Giordano, Christian Lemaire, Tong Li, R John Kimoff, Basil J Petrof
BACKGROUND: Short-term intermittent hypoxia (IH) is common in patients with acute respiratory disorders. Although prolonged exposure to hypoxia induces atrophy and increased fatigability of skeletal muscle, the response to short-term IH is less well known. We hypothesized that the diaphragm and limb muscles would adapt differently to short-term IH given that hypoxia stimulates ventilation and triggers a superimposed exercise stimulus in the diaphragm. METHODS: We determined the structural, metabolic, and contractile properties of the mouse diaphragm after 4 days of IH (8 hours per day, 30 episodes per hour to a FiO2 nadir=6%), and compared responses in the diaphragm to a commonly studied reference limb muscle, the tibialis anterior...
2015: PloS One
Jesus Prieto-Lloret, Maria Ramirez, Elena Olea, Javier Moral-Sanz, Angel Cogolludo, Javier Castañeda, Sara Yubero, Teresa Agapito, Angela Gomez-Niño, Asuncion Rocher, Ricardo Rigual, Ana Obeso, Francisco Perez-Vizcaino, Constancio González
KEY POINTS: Adult animals that have been perinatally exposed to oxygen-rich atmospheres (hyperoxia), recalling those used for oxygen therapy in infants, exhibit a loss of hypoxic pulmonary vasoconstriction, whereas vasoconstriction elicited by depolarizing agents is maintained. Loss of pulmonary hypoxic vasoconstriction is not linked to alterations in oxygen-sensitive K(+) currents in pulmonary artery smooth muscle cells. Loss of hypoxic vasoconstriction is associated with early postnatal oxidative damage and corrected by an antioxidant diet...
June 1, 2015: Journal of Physiology
Portia Thurmond, Jing-Hua Yang, Yedan Li, Lori B Lerner, Kazem M Azadzoi
PURPOSE: Clinical studies have reported a correlation between pelvic ischemia and voiding dysfunction in elderly men. The aim of this study was to identify and compare prostate structural modifications in cultured cells and in a rabbit model after exposure to hypoxia, oxidative stress, and chronic ischemia. MATERIALS AND METHODS: Cultured human prostate smooth muscle cells (SMCs), epithelial cells (ECs), and stromal cells (SCs) were incubated under normoxia, hypoxia, and oxidative stress conditions by use of a computerized oxycycler system...
March 2015: Korean Journal of Urology
H C Heitkamp
Blood flow restriction training has proven to be effective, but it is not well known and is limited by initially producing discomfort. Blood flow restriction (BFR) induces hypoxia and metabolic effects, as well as reduction of proteolysis and induction of anabolic processes. Growth hormone levels are regularly increased. Controversies exist concerning neuromuscular effects. Twenty-eight of 30 studies, showed an increase in strength usually associated with muscle hypertrophy in both men and women, although data for women are sparse...
May 2015: Journal of Sports Medicine and Physical Fitness
Andreia F Fernandes, Heather Fenton, Shannon Martinson, Marion Desmarchelier, Shannon T Ferrell
An approximately 6-mo-old female bald eagle (Haliaeetus leucocephalus) was presented for an inability to fly and bilateral drooped wings. Pectoral muscle atrophy with a moderate polycythemia was present. Over the course of 3 wk, there were no improvements in flight capacity, although the bird gained substantial weight. Further investigation revealed a prominent cyanosis that was responsive to oxygen therapy, a chronic respiratory acidosis with hypoxia, a cardiac murmur, and a persistent polycythemia. No obvious antemortem etiology for the clinical findings was discovered on computerized tomography, angiography, or echocardiography...
December 2014: Journal of Zoo and Wildlife Medicine: Official Publication of the American Association of Zoo Veterinarians
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