Effects of ?-guanidinopropionic acid-feeding on the patterns of myosin isoforms in rat fast-twitch muscle

Ren, Jian; Ohira, Yoshinobu; Holloszy, John O.; Hämäläinen, Nina; Traub, Irmtrub; Pette, Dirk

doi:10.1007/bf00373914

Cited by 28 publications

(25 citation statements)

References 28 publications

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“…The exact mechanisms underlying fiber-type transitions remain to be elucidated and the control of the expression of genes encoding contractile and metabolic proteins has not been clearly identified to date. Previous studies showed that chronic administration of ␤-guanidinopropionic acid, a chemical that decreases the PCr/ATP ratio in muscle, induced a switch from fast to slow myosin isoforms (30). The results of the present study are in accordance with these findings and suggest that the energy potential of muscle fibers could play a regulatory role in determining the muscle phenotype (31).…”

Section: Discussionsupporting

confidence: 91%

High Level of Uncoupling Protein 1 Expression in Muscle of Transgenic Mice Selectively Affects Muscles at Rest and Decreases Their IIb Fiber Content

Couplan

Gelly

Goubern³

et al. 2002

Journal of Biological Chemistry

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The mitochondrial uncoupling protein of brown adipose tissue (UCP1) was expressed in skeletal muscle and heart of transgenic mice at levels comparable with the amount found in brown adipose tissue mitochondria. These transgenic mice have a lower body weight, and when related to body weight, food intake and energy expenditure are increased. A specific reduction of muscle mass was observed but varied according to the contractile activity of muscles. Heart and soleus muscle are unaffected, indicating that muscles undergoing regular contractions, and therefore with a continuous mitochondrial ATP production, are protected. In contrast, the gastrocnemius and plantaris muscles showed a severely reduced mass and a fast to slow shift in fiber types promoting mainly IIa and IIx fibers at the expense of fastest and glycolytic type IIb fibers. These observations are interpreted as a consequence of the strong potential dependence of the UCP1 protonophoric activity, which ensures a negligible proton leak at the membrane potential observed when mitochondrial ATP production is intense. Therefore UCP1 is not deleterious for an intense mitochondrial ATP production and this explains the tolerance of the heart to a high expression level of UCP1. In muscles at rest, where ATP production is low, the rise in membrane potential enhances UCP1 activity. The proton return through UCP1 mimics the effect of a sustained ATP production, permanently lowering mitochondrial membrane potential. This very likely constitutes the origin of the signal leading to the transition in fiber types at rest. Uncoupling protein 1 (UCP1)1 is expressed exclusively in brown adipose tissue (reviewed in Refs. 1 and 2). Its presence in brown fat mitochondria is responsible for heat production by the mitochondria in brown adipocytes. UCP1 allows return of protons into the matrix without ATP synthesis, and therefore dissipates the proton electrochemical gradient built up after proton pumping by the respiratory complexes. When this gradient reaches high values this makes proton pumping and thus substrate oxidation less easy and therefore slows down respiration. Activity of UCP1 prevents this rise of the proton gradient and therefore allows respiration to occur at a high rate, without phosphorylation of ADP into ATP, and therefore energy is instantaneously released as heat. The essential role of the UCP1 in thermogenesis is illustrated by the cold intolerance of mice whose ucp1 gene has been disrupted (3). Recently, two genes coding for proteins highly homologous to UCP1 have been described (reviewed in Refs. 4 -6). Although there are experimental evidence supporting the hypothesis of an uncoupling activity of these proteins (7,8), their physiological relevance is still incompletely resolved (9 -11). We intended to obtain transgenic mice overexpressing the UCP1 in skeletal muscles, with the aim of examining the effects of the presence of this uncoupling protein on the pattern of myosin expression and metabolic characteristics of locomotor muscles. Two other reports pub...

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Section: Discussionsupporting

confidence: 91%

High Level of Uncoupling Protein 1 Expression in Muscle of Transgenic Mice Selectively Affects Muscles at Rest and Decreases Their IIb Fiber Content

Couplan

Gelly

Goubern³

et al. 2002

Journal of Biological Chemistry

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“…muscles of ␤-GPA-fed rats were lower than in the control rats, as reported previously [6,[10][11][14][15][16][17][18]. In contrast, high-energy phosphate levels were elevated in the creatine-fed group.…”

Section: Discussionsupporting

confidence: 84%

Metabolic Modulation of Muscle Fiber Properties Unrelated to Mechanical Stimuli

Ohira

Kawano

Roy

et al. 2003

JJP

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“…In this context, it is also of interest that fast-to-slow transitions in myosin expression have been observed in Cr-depleted fast-twitch muscles of mouse [16] and rat [1,22]. Under these conditions, where the metabolic state of the muscle was directly manipulated, myosin light and heavy chain expression were found to be shifted towards slower isoforms.…”

Section: Discussionmentioning

confidence: 93%

Energy state and myosin heavy chain isoforms in single fibres of normal and transforming rabbit muscles

Conjard

Peuker

Pette

1998

Pfl�gers Archiv European Journal of Physiology

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Energy-rich phosphates, [ATP]/[ADPfree] ratios, and the myosin heavy chain (MHC) complement were determined in single fibres from normal rabbit muscles, and in fibres isolated from tibialis anterior muscle undergoing fast-to-slow conversion by chronic low-frequency stimulation (CLFS). In normal muscles, energy-rich phosphate contents and [ATP]/[ADPfree] ratios could thus be assigned to different MHC-based fibre types. Phosphocreatine (PCr) contents and [ATP]/[ADPfree] ratios differed markedly between fast- and slow-twitch fibres, as well as within the fast fibre subtypes. Both magnitudes were approximately twofold higher in the fastest (type IIB) fibres as compared to the slowest (type I) fibres. According to PCr contents and [ATP]/[ADPfree] ratios pure and hybrid fibres were aligned in an order similar to that determined by their contractile properties and myofibrillar ATPase activities. CLFS for up to 30 days induced pronounced decreases in PCr and [ATP]/[ADPfree] which attained levels twofold lower than in normal slow-twitch fibres. In both normal and stimulated muscles, PCr and [ATP]/[ADPfree] ratios were correlated, indicating their equilibrium in the different fibre types. The relationship detected between MHC isoform expression and the [ATP]/[ADPfree] ratio suggests that the drastic and persistent depression of the cellular energy state may act as an important signal initiating fast-to-slow transformation processes in muscle fibres.

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Effects of ?-guanidinopropionic acid-feeding on the patterns of myosin isoforms in rat fast-twitch muscle

Cited by 28 publications

References 28 publications

High Level of Uncoupling Protein 1 Expression in Muscle of Transgenic Mice Selectively Affects Muscles at Rest and Decreases Their IIb Fiber Content

High Level of Uncoupling Protein 1 Expression in Muscle of Transgenic Mice Selectively Affects Muscles at Rest and Decreases Their IIb Fiber Content

Metabolic Modulation of Muscle Fiber Properties Unrelated to Mechanical Stimuli

Energy state and myosin heavy chain isoforms in single fibres of normal and transforming rabbit muscles

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