Phase-modulated rotating-frame imaging of phosphorus metabolites in skeletal muscle in vivo

1987 ◽  
Vol 15 (5) ◽  
pp. 869-870
Author(s):  
MARTIN J. BLACKLEDGE ◽  
R. A. JOHN CHALLISS ◽  
GEORGE K. RADDA
2001 ◽  
Vol 281 (2) ◽  
pp. H882-H887 ◽  
Author(s):  
Sam Hitchins ◽  
Julie M. Cieslar ◽  
Geoffrey P. Dobson

The aim of this study was to examine two methods of 31P NMR quantitation of phosphocreatine (PCr), ATP, and Pi in rat heart and skeletal muscle in vivo. The first method employed an external standard of phenylphosphonic acid (PPA; 10 mM), and the second method used an enzymatic measurement of tissue ATP equated to the area under the βATP peak. With the use of the external standard, the concentrations of ATP, PCr, and Pi in the rat heart were 4.48 ± 0.33, 9.21 ± 0.65, and 2.25 ± 0.16 μmol/g wet wt, respectively. With the use of the internal ATP standard, measured on the same tissue, the contents (means ± SE) were 4.78 ± 0.19, 9.83 ± 0.18, and 2.51 ± 0.33 μmol/g wet wt, respectively ( n = 7). In skeletal muscle, ATP, PCr, and Pi were 6.09 ± 0.19, 23.44 ± 0.88, and 1.81 ± 0.18 μmol/g wet wt using the PPA standard and 6.03 ± 0.19, 23.30 ± 1.30, and 1.82 ± 0.19 μmol/g wet wt using the internal ATP standard ( n = 6). There was no significant difference for each metabolite as measured by the two methods of quantification in heart or skeletal muscle. The results validate the use of an external reference positioned symmetrically above the coil and imply that each has similar NMR sensitivities (similar signal amplitude per mole of 31P between PPA and tissue phosphorus compounds). We conclude that PCr, ATP, and Pi are nearly 100% visible in the normoxic heart and nonworking skeletal muscle given the errors of measurement.


1986 ◽  
Vol 69 (2) ◽  
pp. 331-336
Author(s):  
Martin J Blackledge ◽  
David J Hayes ◽  
R.A.John Challiss ◽  
George K Radda

2020 ◽  
Vol 4 (1) ◽  
Author(s):  
Bruno Paun ◽  
Daniel García Leon ◽  
Alex Claveria Cabello ◽  
Roso Mares Pages ◽  
Elena de la Calle Vargas ◽  
...  

Abstract Background Skeletal muscle injury characterisation during healing supports trauma prognosis. Given the potential interest of computed tomography (CT) in muscle diseases and lack of in vivo CT methodology to image skeletal muscle wound healing, we tracked skeletal muscle injury recovery using in vivo micro-CT in a rat model to obtain a predictive model. Methods Skeletal muscle injury was performed in 23 rats. Twenty animals were sorted into five groups to image lesion recovery at 2, 4, 7, 10, or 14 days after injury using contrast-enhanced micro-CT. Injury volumes were quantified using a semiautomatic image processing, and these values were used to build a prediction model. The remaining 3 rats were imaged at all monitoring time points as validation. Predictions were compared with Bland-Altman analysis. Results Optimal contrast agent dose was found to be 20 mL/kg injected at 400 μL/min. Injury volumes showed a decreasing tendency from day 0 (32.3 ± 12.0mm3, mean ± standard deviation) to day 2, 4, 7, 10, and 14 after injury (19.6 ± 12.6, 11.0 ± 6.7, 8.2 ± 7.7, 5.7 ± 3.9, and 4.5 ± 4.8 mm3, respectively). Groups with single monitoring time point did not yield significant differences with the validation group lesions. Further exponential model training with single follow-up data (R2 = 0.968) to predict injury recovery in the validation cohort gave a predictions root mean squared error of 6.8 ± 5.4 mm3. Further prediction analysis yielded a bias of 2.327. Conclusion Contrast-enhanced CT allowed in vivo tracking of skeletal muscle injury recovery in rat.


Metabolites ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 481
Author(s):  
Gemma G. Martínez-García ◽  
Raúl F. Pérez ◽  
Álvaro F. Fernández ◽  
Sylvere Durand ◽  
Guido Kroemer ◽  
...  

Autophagy is an essential protective mechanism that allows mammalian cells to cope with a variety of stressors and contributes to maintaining cellular and tissue homeostasis. Due to these crucial roles and also to the fact that autophagy malfunction has been described in a wide range of pathologies, an increasing number of in vivo studies involving animal models targeting autophagy genes have been developed. In mammals, total autophagy inactivation is lethal, and constitutive knockout models lacking effectors of this route are not viable, which has hindered so far the analysis of the consequences of a systemic autophagy decline. Here, we take advantage of atg4b−/− mice, an autophagy-deficient model with only partial disruption of the process, to assess the effects of systemic reduction of autophagy on the metabolome. We describe for the first time the metabolic footprint of systemic autophagy decline, showing that impaired autophagy results in highly tissue-dependent alterations that are more accentuated in the skeletal muscle and plasma. These changes, which include changes in the levels of amino-acids, lipids, or nucleosides, sometimes resemble those that are frequently described in conditions like aging, obesity, or cardiac damage. We also discuss different hypotheses on how impaired autophagy may affect the metabolism of several tissues in mammals.


Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1791
Author(s):  
Rosa Scala ◽  
Fatima Maqoud ◽  
Nicola Zizzo ◽  
Giuseppe Passantino ◽  
Antonietta Mele ◽  
...  

(1) Background: Cantu syndrome (CS) arises from gain-of-function (GOF) mutations in the ABCC9 and KCNJ8 genes, which encode ATP-sensitive K+ (KATP) channel subunits SUR2 and Kir6.1, respectively. Most CS patients have mutations in SUR2, the major component of skeletal muscle KATP, but the consequences of SUR2 GOF in skeletal muscle are unknown. (2) Methods: We performed in vivo and ex vivo characterization of skeletal muscle in heterozygous SUR2[A478V] (SUR2wt/AV) and homozygous SUR2[A478V] (SUR2AV/AV) CS mice. (3) Results: In SUR2wt/AV and SUR2AV/AV mice, forelimb strength and diaphragm amplitude movement were reduced; muscle echodensity was enhanced. KATP channel currents recorded in Flexor digitorum brevis fibers showed reduced MgATP-sensitivity in SUR2wt/AV, dramatically so in SUR2AV/AV mice; IC50 for MgATP inhibition of KATP currents were 1.9 ± 0.5 × 10−5 M in SUR2wt/AV and 8.6 ± 0.4 × 10−6 M in WT mice and was not measurable in SUR2AV/AV. A slight rightward shift of sensitivity to inhibition by glibenclamide was detected in SUR2AV/AV mice. Histopathological and qPCR analysis revealed atrophy of soleus and tibialis anterior muscles and up-regulation of atrogin-1 and MuRF1 mRNA in CS mice. (4) Conclusions: SUR2[A478V] “knock-in” mutation in mice impairs KATP channel modulation by MgATP, markedly so in SUR2AV/AV, with atrophy and non-inflammatory edema in different skeletal muscle phenotypes.


Bone ◽  
2021 ◽  
pp. 116029
Author(s):  
Taro Fujimaki ◽  
Takashi Ando ◽  
Takanori Hata ◽  
Yoshihiro Takayama ◽  
Tetsuro Ohba ◽  
...  

Function ◽  
2021 ◽  
Author(s):  
Leslie M Baehr ◽  
David C Hughes ◽  
Sarah A Lynch ◽  
Delphi Van Haver ◽  
Teresa Mendes Maia ◽  
...  

Abstract MuRF1 (TRIM63) is a muscle-specific E3 ubiquitin ligase and component of the ubiquitin proteasome system. MuRF1 is transcriptionally upregulated under conditions that cause muscle loss, in both rodents and humans, and is a recognized marker of muscle atrophy. In this study, we used in vivo electroporation to determine if MuRF1 overexpression alone can cause muscle atrophy and, in combination with ubiquitin proteomics, identify the endogenous MuRF1 substrates in skeletal muscle. Overexpression of MuRF1 in adult mice increases ubiquitination of myofibrillar and sarcoplasmic proteins, increases expression of genes associated with neuromuscular junction instability, and causes muscle atrophy. A total of 169 ubiquitination sites on 56 proteins were found to be regulated by MuRF1. MuRF1-mediated ubiquitination targeted both thick and thin filament contractile proteins, as well as, glycolytic enzymes, deubiquitinases, p62, and VCP. These data reveal a potential role for MuRF1 in not only the breakdown of the sarcomere, but also the regulation of metabolism and other proteolytic pathways in skeletal muscle.


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