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9. Spaceflight effects on single skeletal muscle fiber function in the rhesus monkey

Author

Fitts, R. H, Desplanches, D, Romatowski, J. G, and Widrick, J. J

Subjects
Life Sciences (General)
Abstract

The purpose of this investigation was to understand how 14 days of weightlessness alters the cellular properties of individual slow- and fast-twitch muscle fibers in the rhesus monkey. The diameter of the soleus (Sol) type I, medial gastrocnemius (MG) type I, and MG type II fibers from the vivarium controls averaged 60 +/- 1, 46 +/- 2, and 59 +/- 2 microm, respectively. Both a control 1-G capsule sit (CS) and spaceflight (SF) significantly reduced the Sol type I fiber diameter (20 and 13%, respectively) and peak force, with the latter declining from 0.48 +/- 0.01 to 0.31 +/- 0.02 (CS group) and 0.32 +/- 0.01 mN (SF group). When the peak force was expressed as kiloNewtons per square meter (kN/m(2)), only the SF group showed a significant decline. This group also showed a significant 15% drop in peak fiber stiffness that suggests that fewer cross bridges were contracting in parallel. In the MG, SF but not CS depressed the type I fiber diameter and force. Additionally, SF significantly depressed absolute (mN) and relative (kN/m(2)) force in the fast-twitch MG fibers by 30% and 28%, respectively. The Ca(2+) sensitivity of the type I fiber (Sol and MG) was significantly reduced by growth but unaltered by SF. Flight had no significant effect on the mean maximal fiber shortening velocity in any fiber type or muscle. The post-SF Sol type I fibers showed a reduced peak power and, at peak power, an elevated velocity and decreased force. In conclusion, CS and SF caused atrophy and a reduced force and power in the Sol type I fiber. However, only SF elicited atrophy and reduced force (mN) in the MG type I fiber and a decline in relative force (kN/m(2)) in the Sol type I and MG type II fibers.

Published
2000

10. Effect of spaceflight on the maximal shortening velocity, morphology, and enzyme profile of fast- and slow-twitch skeletal muscle fibers in rhesus monkeys

Author

Fitts, R. H, Romatowski, J. G, De La Cruz, L, Widrick, J. J, and Desplanches, D

Subjects
Life Sciences (General)
Abstract

Weightlessness has been shown to cause limb muscle wasting and a reduced peak force and power in the antigravity soleus muscle. Despite a reduced peak power, Caiozzo et al. observed an increased maximal shortening velocity in the rat soleus muscle following a 14-day space flight. The major purpose of the present investigation was to determine if weightlessness induced an elevated velocity in the antigravity slow type I fibers of the rhesus monkey (Macaca mulatta), as well as to establish a cellular mechanism for the effect. Spaceflight or models of weightlessness have been shown to increase glucose uptake, elevate muscle glycogen content, and increase fatigability of the soleus muscle. The latter appears to be in part caused by a reduced ability of the slow oxidative fibers to oxidize fats. A second goal of this study was to establish the extent to which weightlessness altered the substrate profile and glycolytic and oxidative enzyme capacity of individual slow- and fast-twitch fibers.

Published
2000

18. Mechanotransduction in striated muscle via focal adhesion kinase

Author

Durieux, AC, Desplanches, D, Freyssenet, O, Flück, M, Durieux, AC, Desplanches, D, Freyssenet, O, and Flück, M

Abstract

Contractile tissues demonstrate a pronounced capacity to remodel their composition in response to mechanical challenges. Descriptive evidence suggests the upstream involvement of the phosphotransfer enzyme FAK (focal adhesion kinase) in the molecular control of load-dependent muscle plasticity. Thereby FAK evolves as a myocellular transducer of mechanical signals towards downstream transcript expression in myofibres. Recent advances in somatic gene therapy now allow the exploration of the functional involvement of this enzyme in mechanotransduction in intact muscle. ©The Authors.

Published
2007

46. Effect of spaceflight on the maximal shortening velocity, morphology, and enzyme profile of fast- and slow-twitch skeletal muscle fibers in rhesus monkeys

Author

Robert Fitts, Jg, Romatowski, De La Cruz L, Jj, Widrick, and Desplanches D

Subjects
Male, Muscle Fibers, Slow-Twitch, Myosin Light Chains, Myosin Heavy Chains, Weightlessness, Muscle Fibers, Fast-Twitch, Animals, Space Flight, Muscle, Skeletal, Macaca mulatta, Glycogen
Abstract

Weightlessness has been shown to cause limb muscle wasting and a reduced peak force and power in the antigravity soleus muscle. Despite a reduced peak power, Caiozzo et al. observed an increased maximal shortening velocity in the rat soleus muscle following a 14-day space flight. The major purpose of the present investigation was to determine if weightlessness induced an elevated velocity in the antigravity slow type I fibers of the rhesus monkey (Macaca mulatta), as well as to establish a cellular mechanism for the effect. Spaceflight or models of weightlessness have been shown to increase glucose uptake, elevate muscle glycogen content, and increase fatigability of the soleus muscle. The latter appears to be in part caused by a reduced ability of the slow oxidative fibers to oxidize fats. A second goal of this study was to establish the extent to which weightlessness altered the substrate profile and glycolytic and oxidative enzyme capacity of individual slow- and fast-twitch fibers.

50. AMPKα1-LDH pathway regulates muscle stem cell self-renewal by controlling metabolic homeostasis.

Author

Theret M, Gsaier L, Schaffer B, Juban G, Ben Larbi S, Weiss-Gayet M, Bultot L, Collodet C, Foretz M, Desplanches D, Sanz P, Zang Z, Yang L, Vial G, Viollet B, Sakamoto K, Brunet A, Chazaud B, and Mounier R

Subjects
Animals, Glycolysis, Mice, Mice, Knockout, AMP-Activated Protein Kinases metabolism, Cell Differentiation, Cell Self Renewal, Homeostasis, L-Lactate Dehydrogenase metabolism, Muscles cytology, Stem Cells metabolism
Abstract

Control of stem cell fate to either enter terminal differentiation versus returning to quiescence (self-renewal) is crucial for tissue repair. Here, we showed that AMP-activated protein kinase (AMPK), the master metabolic regulator of the cell, controls muscle stem cell (MuSC) self-renewal. AMPKα1 -/- MuSCs displayed a high self-renewal rate, which impairs muscle regeneration. AMPKα1 -/- MuSCs showed a Warburg-like switch of their metabolism to higher glycolysis. We identified lactate dehydrogenase (LDH) as a new functional target of AMPKα1. LDH, which is a non-limiting enzyme of glycolysis in differentiated cells, was tightly regulated in stem cells. In functional experiments, LDH overexpression phenocopied AMPKα1 -/- phenotype, that is shifted MuSC metabolism toward glycolysis triggering their return to quiescence, while inhibition of LDH activity rescued AMPKα1 -/- MuSC self-renewal. Finally, providing specific nutrients (galactose/glucose) to MuSCs directly controlled their fate through the AMPKα1/LDH pathway, emphasizing the importance of metabolism in stem cell fate., (© 2017 The Authors.)

Published
2017
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