scholarly journals Microproteins in skeletal muscle: hidden keys in muscle physiology

Author(s):  
Bernardo Bonilauri ◽  
Bruno Dallagiovanna
Cell Calcium ◽  
2018 ◽  
Vol 76 ◽  
pp. 101-115 ◽  
Author(s):  
Antonio Michelucci ◽  
Maricela García-Castañeda ◽  
Simona Boncompagni ◽  
Robert T. Dirksen

2019 ◽  
Vol 3 ◽  
pp. 147 ◽  
Author(s):  
Lucy A. Oakey ◽  
Rachel S. Fletcher ◽  
Yasir S. Elhassan ◽  
David M. Cartwright ◽  
Craig L. Doig ◽  
...  

Background: Skeletal muscle is central to whole body metabolic homeostasis, with age and disease impairing its ability to function appropriately to maintain health. Inadequate NAD+ availability is proposed to contribute to pathophysiology by impairing metabolic energy pathway use. Despite the importance of NAD+ as a vital redox cofactor in energy production pathways being well-established, the wider impact of disrupted NAD+ homeostasis on these pathways is unknown. Methods: We utilised skeletal muscle myotube models to induce NAD+ depletion, repletion and excess and conducted metabolic tracing to provide comprehensive and detailed analysis of the consequences of altered NAD+ metabolism on central carbon metabolic pathways. We used stable isotope tracers, [1,2-13C] D-glucose and [U-13C] glutamine, and conducted combined 2D-1H,13C-heteronuclear single quantum coherence (HSQC) NMR spectroscopy and GC-MS analysis. Results: NAD+ excess driven by nicotinamide riboside (NR) supplementation within skeletal muscle cells resulted in enhanced nicotinamide clearance, but had no effect on energy homeostasis or central carbon metabolism. Nicotinamide phosphoribosyltransferase (NAMPT) inhibition induced NAD+ depletion and resulted in equilibration of metabolites upstream of glyceraldehyde phosphate dehydrogenase (GAPDH). Aspartate production through glycolysis and TCA cycle activity was increased in response to low NAD+, which was rapidly reversed with repletion of the NAD+ pool using NR. NAD+ depletion reversibly inhibits cytosolic GAPDH activity, but retains mitochondrial oxidative metabolism, suggesting differential effects of this treatment on sub-cellular pyridine pools. When supplemented, NR efficiently reversed these metabolic consequences. However, the functional relevance of increased aspartate levels after NAD+ depletion remains unclear, and requires further investigation. Conclusions: These data highlight the need to consider carbon metabolism and clearance pathways when investigating NAD+ precursor usage in models of skeletal muscle physiology.


2010 ◽  
Vol 189 (1) ◽  
pp. 95-109 ◽  
Author(s):  
David S. Gokhin ◽  
Raymond A. Lewis ◽  
Caroline R. McKeown ◽  
Roberta B. Nowak ◽  
Nancy E. Kim ◽  
...  

During myofibril assembly, thin filament lengths are precisely specified to optimize skeletal muscle function. Tropomodulins (Tmods) are capping proteins that specify thin filament lengths by controlling actin dynamics at pointed ends. In this study, we use a genetic targeting approach to explore the effects of deleting Tmod1 from skeletal muscle. Myofibril assembly, skeletal muscle structure, and thin filament lengths are normal in the absence of Tmod1. Tmod4 localizes to thin filament pointed ends in Tmod1-null embryonic muscle, whereas both Tmod3 and -4 localize to pointed ends in Tmod1-null adult muscle. Substitution by Tmod3 and -4 occurs despite their weaker interactions with striated muscle tropomyosins. However, the absence of Tmod1 results in depressed isometric stress production during muscle contraction, systemic locomotor deficits, and a shift to a faster fiber type distribution. Thus, Tmod3 and -4 compensate for the absence of Tmod1 structurally but not functionally. We conclude that Tmod1 is a novel regulator of skeletal muscle physiology.


2008 ◽  
pp. 49-69 ◽  
Author(s):  
Michael Kjr ◽  
Hannu Kalimo ◽  
Bengt Saltin

2020 ◽  
Vol 129 (6) ◽  
pp. 1405-1412
Author(s):  
Sydnee A. Hyman ◽  
Mackenzie B. Norman ◽  
Shanelle N. Dorn ◽  
Shannon N. Bremner ◽  
Mary C. Esparza ◽  
...  

We introduce an improved method to assess rabbit supraspinatus muscle physiology. Maximum isometric force measured for the rabbit supraspinatus was dramatically greater than previous reports in the literature. Consequently, the isometric contractile stress reported is almost 10 times greater than previous reports of rabbit supraspinatus, but similar to available literature of other mammalian skeletal muscle. We show that previous reports of peak supraspinatus isometric force were subphysiological by ∼90%


2019 ◽  
Vol 43 (1) ◽  
pp. 69-75
Author(s):  
Scott Medler

Frogs are routinely used in physiology teaching laboratories to demonstrate important physiological processes. There have been recent directives that promote the use of the anesthetic MS-222 (tricaine methanesulfonate), rather than lowering body temperature with a cold water bath to prepare reptiles and amphibians for physiological experiments or euthanasia. Indeed, the most recent edition of the American Veterinary Medical Association (AVMA) Guidelines for the Euthanasia of Animals proclaims that chilling in water is not an appropriate method and advocates for the usage of MS-222 or other anesthetics. However, prominent researchers have responded to this position by highlighting evidence that cooling ectothermic vertebrates is, in fact, an effective and appropriate method. Furthermore, MS-222 is a known voltage-gated Na+ channel blocker, and this anesthetic’s impact on the physiology of excitable tissues suggests that its use might be incompatible with experiments on nerve and muscle tissues. In the present study, I examined the effects of MS-222 at a concentration of 1.5 g/l on nerve, skeletal muscle, and cardiac muscle physiology of frogs. I found that immersion of frogs in this anesthetic blocked basic nerve and muscle physiology, making the frogs unsuitable for laboratory experiments. Applying MS-222 directly to the sciatic nerve dramatically blocked normal excitation-contraction coupling in skeletal muscle preparations, and direct application to the heart caused the organs to stop contracting. Based on these results, I conclude that MS-222 at the concentration studied may be incompatible with physiological preparations that rely on electrically excitable tissues for their normal function. Physiology educators who must use MS-222 with frogs should empirically determine an appropriate dosage and recovery time before using the anesthetic in the teaching laboratory.


2019 ◽  
Vol 43 (4) ◽  
pp. 467-471 ◽  
Author(s):  
Anandit John Mathew ◽  
Mahatabb Nundy ◽  
Niranjini Chandrashekaran ◽  
Vinay Oommen

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