Dataset Information

Hypoxia Resistance Is an Inherent Phenotype of the Mouse Flexor Digitorum Brevis Skeletal Muscle.

ABSTRACT: The various functions of skeletal muscle (movement, respiration, thermogenesis, etc.) require the presence of oxygen (O₂). Inadequate O₂ bioavailability (ie, hypoxia) is detrimental to muscle function and, in chronic cases, can result in muscle wasting. Current therapeutic interventions have proven largely ineffective to rescue skeletal muscle from hypoxic damage. However, our lab has identified a mammalian skeletal muscle that maintains proper physiological function in an environment depleted of O₂. Using mouse models of in vivo hindlimb ischemia and ex vivo anoxia exposure, we observed the preservation of force production in the flexor digitorum brevis (FDB), while in contrast the extensor digitorum longus (EDL) and soleus muscles suffered loss of force output. Unlike other muscles, we found that the FDB phenotype is not dependent on mitochondria, which partially explains the hypoxia resistance. Muscle proteomes were interrogated using a discovery-based approach, which identified significantly greater expression of the transmembrane glucose transporter GLUT1 in the FDB as compared to the EDL and soleus. Through loss-and-gain-of-function approaches, we determined that GLUT1 is necessary for the FDB to survive hypoxia, but overexpression of GLUT1 was insufficient to rescue other skeletal muscles from hypoxic damage. Collectively, the data demonstrate that the FDB is uniquely resistant to hypoxic insults. Defining the mechanisms that explain the phenotype may provide insight towards developing approaches for preventing hypoxia-induced tissue damage.

SUBMITTER: Amorese AJ

PROVIDER: S-EPMC10165545 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Hypoxia Resistance Is an Inherent Phenotype of the Mouse Flexor Digitorum Brevis Skeletal Muscle.

Amorese Adam J AJ Minchew Everett C EC Tarpey Michael D MD Readyoff Andrew T AT Williamson Nicholas C NC Schmidt Cameron A CA McMillin Shawna L SL Goldberg Emma J EJ Terwilliger Zoe S ZS Spangenburg Quincy A QA Witczak Carol A CA Brault Jeffrey J JJ Abel E Dale ED McClung Joseph M JM Fisher-Wellman Kelsey H KH Spangenburg Espen E EE

Function (Oxford, England) 20230321 3

The various functions of skeletal muscle (movement, respiration, thermogenesis, etc.) require the presence of oxygen (O<sub>2</sub>). Inadequate O<sub>2</sub> bioavailability (ie, hypoxia) is detrimental to muscle function and, in chronic cases, can result in muscle wasting. Current therapeutic interventions have proven largely ineffective to rescue skeletal muscle from hypoxic damage. However, our lab has identified a mammalian skeletal muscle that maintains proper physiological function in an ...[more]

PMID: 37168496

Similar Datasets

Project description:Duchenne muscular dystrophy is due to genetic abnormalities in the dystrophin gene and represents one of the most frequent genetic childhood diseases. In the X-linked muscular dystrophy (mdx) mouse model of dystrophinopathy, different subtypes of skeletal muscles are affected to a varying degree albeit the same single base substitution within exon 23 of the dystrophin gene. Thus, to determine potential muscle subtype-specific differences in secondary alterations due to a deficiency in dystrophin, in this study, we carried out a comparative histological and proteomic survey of mdx muscles. We intentionally included the skeletal muscles that are often used for studying the pathomechanism of muscular dystrophy. Histological examinations revealed a significantly higher degree of central nucleation in the soleus and extensor digitorum longus muscles compared with the flexor digitorum brevis and interosseus muscles. Muscular hypertrophy of 20-25% was likewise only observed in the soleus and extensor digitorum longus muscles from mdx mice, but not in the flexor digitorum brevis and interosseus muscles. For proteomic analysis, muscle protein extracts were separated by fluorescence two-dimensional (2D) gel electrophoresis. Proteins with a significant change in their expression were identified by mass spectrometry. Proteomic profiling established an altered abundance of 24, 17, 19 and 5 protein species in the dystrophin-deficient soleus, extensor digitorum longus, flexor digitorum brevis and interosseus muscle, respectively. The key proteomic findings were verified by immunoblot analysis. The identified proteins are involved in the contraction-relaxation cycle, metabolite transport, muscle metabolism and the cellular stress response. Thus, histological and proteomic profiling of muscle subtypes from mdx mice indicated that distinct skeletal muscles are differentially affected by the loss of the membrane cytoskeletal protein, dystrophin. Varying degrees of perturbed protein expression patterns in the muscle subtypes from mdx mice may be due to dissimilar downstream events, including differences in muscle structure or compensatory mechanisms that counteract pathophysiological processes. The interosseus muscle from mdx mice possibly represents a naturally protected phenotype.

Project description:BackgroundCarpal tunnel syndrome (CTS) is by far the most common entrapment neuropathy (Adams et al. Am J Ind Med 25:527-536, 1994; Cheadle et al. Am J Public Health 84:190-196, 1994; Stevens et al. Neurology 38:134-138, 1988). A combination of described symptoms, clinical findings and electrophysiological testing is used to confirm the diagnosis. Several studies have suggested that in patients with a clinical diagnosis of CTS, the accuracy of nerve sonography is similar to that for electromyography (Chen et al. BMC Med Imaging 11:22, 2011; Guan et al. Neurol Res 33:970-953, 2011; Kele et al. Neurology 61:389-391, 2003; Tai et al. Ultrasound Med Biol 38:1121-1128, 2012). In special cases though, the nerve sonography can reveal the cause of the median entrapment neuropathy (Fumière et al. JBR-BTR 85:1-3, 2002; Kele et al. J Neurosurg 97:471-473, 2002; Kele et al. Neurology 61:389-391, 2003; Zamora et al. J Clin Ultrasound 39:44-47, 2011).MethodsA 43-year-old farmer was admitted to our department with 1 year of intermittent pain in the left hand and numbness of the thumb, index and middle finger. The pain and the numbness could be reproduced by extension of the wrist and fingers. The electrophysiological testing revealed signs of an entrapment median neuropathy in carpal tunnel.ResultsThe high-resolution sonography (18 MHz) revealed signs of entrapment neuropathy with increased cross-sectional area, disturbed echostructure of the nerve and pathological wrist-to-forearm ratio, confirming the results from a similar study (Kele et al. Neurology 61:389-391, 2003). In addition, an elongated muscle belly of the flexor digitorum superficialis in the carpal tunnel could be identified. During the extension of the wrist and fingers, a greater protrusion of the muscle belly could be demonstrated causing compression of the median nerve.ConclusionsWe present a video case report of the sonographic findings of a patient diagnosed with carpal tunnel syndrome due to an elongated muscle belly of the flexor digitorum superficialis in the carpal tunnel. Our case highlights the importance of nerve sonography in the differential diagnosis of the cause of a carpal tunnel syndrome. With the aid of ultrasonography, it is possible to obtain very important information concerning different aspects of this case. First, in showing the presence of the elongated muscle belly of the flexor digitorum superficialis, the cause of the symptoms could be explained. Second, it was possible through the ultrasound study to explain the atypical clinical appearance in this case, demonstrating the compression neuropathy only after extension of the wrist and fingers. There have been no previous reports in which authors described an elongated muscle belly as cause of a CTS. Third, and perhaps most important, ultrasonography had a direct influence on our selection of therapeutical strategy and approach. As a result, we recommended in this patient a surgical therapy to completely solve the problem, but the patient declined this option and preferred a conservative therapy with a hand orthosis to prevent wrist extension. In conclusion we recommend ultrasonography as a very useful method in the diagnostic evaluation of carpal tunnel syndrome. We have clearly demonstrated that ultrasonography can be used to discover the cause of median nerve compression, especially in cases with an atypical clinical presentation.

Dataset Information

Hypoxia Resistance Is an Inherent Phenotype of the Mouse Flexor Digitorum Brevis Skeletal Muscle.

Publications

Hypoxia Resistance Is an Inherent Phenotype of the Mouse Flexor Digitorum Brevis Skeletal Muscle.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets