Protein variants of skeletal muscle regulatory myosin light chain isoforms: prevalence in mammals, generation and transitions during muscle remodelling

González, Blanca; Negredo, Pilar; Hernando, Raquel; Manso, Rafael

doi:10.1007/s004240100702

Cited by 28 publications

(36 citation statements)

References 38 publications

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“…It is well established that the various light and heavy chains of myosin undergo a stepwise replacement from fast to slow isoforms during fibre type shifting [41,42], which has also been shown to occur in the case of regulatory elements of the contractile apparatus, such as the individual subunits of troponin [4]. The expanded views of 2-D landmark spots shown in Fig.…”

Section: Confirmation Of Fast-to-slow Muscle Transition By Contractilmentioning

confidence: 90%

“…An elevation of aerobic-oxidative capacity, decreased fibre calibre and changes in the density of distinct muscle proteins, switches in isoform expression patterns and alterations in proteinprotein interactions are established biochemical and cell biological hallmarks of transformed skeletal muscles. This includes: (i) metabolic pathways such as the citric acid cycle, fatty acid oxidation and the respiratory chain which causes a drastic increase in enzymes of aerobic substrate oxidation [39,40], (ii) the contractile apparatus that undergoes a stepwise replacement of myosin light and heavy chains from fast isoforms to their slower counterparts [41,42], (iii) the ion-regulatory machinery of the excitation-contractionrelaxation cycle with a shift from fast to slower isoforms with respect to the SERCA-type Ca 21 -ATPases, the voltagesensing dihydropyridine receptor, the ryanodine receptor Ca 21 -release channel and various Ca 21 -binding proteins [43,44], (iv) the neuromuscular junction with distinct changes in the acetylcholinesterase and the nicotinic acetylcholine receptor [45,46] and, (v) a decrease in the supramolecular interaction pattern between Ca…”

Section: Introductionmentioning

confidence: 99%

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Proteomic profiling of chronic low‐frequency stimulated fast muscle

et al. 2007

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Skeletal muscle fibre transitions occur in many biological processes, in response to alterations in neuromuscular activity, in muscular disorders, during age-induced muscle wasting and in myogenesis. It was therefore of interest to perform a comprehensive proteomic profiling of muscle transformation. Chronic low-frequency stimulation of the rabbit tibialis anterior muscle represents an established model system for studying the response of fast fibres to enhanced neuromuscular activity under conditions of maximum activation. We have conducted a DIGE analysis of unstimulated control specimens versus 14-and 60-day conditioned muscles. A differential expression pattern was observed for 41 protein species with 29 increased and 12 decreased muscle proteins. Identified classes of proteins that are changed during the fast-to-slow transition process belong to the contractile machinery, ion homeostasis, excitation-contraction coupling, capillarization, metabolism and stress response. Results from immunoblotting agreed with the conversion of the metabolic, regulatory and contractile molecular apparatus to support muscle fibres with slower twitch characteristics. Besides confirming established muscle elements as reliable transition markers, this proteomics-based study has established the actin-binding protein cofilin-2 and the endothelial marker transgelin as novel biomarkers for evaluating muscle transformation.

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Section: Confirmation Of Fast-to-slow Muscle Transition By Contractilmentioning

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Proteomic profiling of chronic low‐frequency stimulated fast muscle

et al. 2007

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“…The proteomic analysis of the age-related transformation of fibres agrees with findings from artificially induced fibre type transitions due to chronic low-frequency stimulation. Fast-to-slow transformation is associated with major alterations in the density and isoform expression pattern of both MHCs (Kirschbaum et al, 1989) and MLCs (Gonzalez et al, 2002). Changes in the expression levels and post-translational modifications of key contractile elements is a clear indication that senescent motor units undergo major physiological adaptations.…”

Section: Discussionmentioning

confidence: 99%

Drastic increase of myosin light chain MLC-2 in senescent skeletal muscle indicates fast-to-slow fibre transition in sarcopenia of old age

Gannon

Doran

Kirwan

et al. 2009

European Journal of Cell Biology

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The age-dependent decline in skeletal muscle mass and function is believed to be due to a multi-factorial pathology and represents a major factor that blocks healthy aging by increasing physical disability, frailty and loss of independence in the elderly. This study has focused on the comparative proteomic analysis of contractile elements and revealed that the most striking age-related changes seem to occur in the protein family representing myosin light chains (MLCs). Comparative screening of total muscle extracts suggests a fast-to-slow transition in the aged MLC population. The mass spectrometric analysis of the myofibril-enriched fraction identified the MLC2 isoform of the slow-type MLC as the contractile protein with the most drastically changed expression during aging. Immunoblotting confirmed an increased abundance of slow MLC2, concomitant with a switch in fast versus slow myosin heavy chains. Staining of two-dimensional gels of crude extracts with the phospho-specific fluorescent dye ProQ-Diamond identified the increased MLC2 spot as a muscle protein with a drastically enhanced phosphorylation level in aged fibres. Comparative immunofluorescence microscopy, using antibodies to fast and slow myosin isoforms, confirmed a fast-to-slow transformation process during muscle aging. Interestingly, the dramatic increase in slow MLC2 expression was restricted to individual senescent fibres. These findings agree with the idea that aged skeletal muscles undergo a shift to more aerobic-oxidative metabolism in a slower-twitching fibre population and suggest the slow MLC2 isoform as a potential biomarker for fibre type shifting in sarcopenia of old age.

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“…Differently expressed isoforms of proteins are the basis of muscle heterogeneity inherent to soleus and gastrocnemius muscles [10,15,[25][26][27]]. In the current study, this was shown by the variation in the relative abundances of MLC isoforms and metabolic enzymes as well as in the presence of parvalbumin in the white portion of gastrocnemius muscle [28].…”

Section: Discussionmentioning

confidence: 53%

Subcellular proteomics of mice gastrocnemius and soleus muscles

Vitorino

Ferreira

Neuparth

et al. 2007

Analytical Biochemistry

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A proteomics characterization of mice soleus and gastrocnemius white portion skeletal muscles was performed using nuclear, mitochondrial/membrane, and cytosolic subcellular fractions. The proposed methodology allowed the elimination of the cytoskeleton proteins from the cytosolic fraction and of basic proteins from the nuclear fraction. The subsequent protein separation by twodimensional gel electrophoresis prior to mass spectrometry analysis allowed the detection of more than 600 spots in each muscle. In the gastrocnemius muscle fractions, it was possible to identify 178 protein spots corresponding to 108 different proteins. In the soleus muscle fractions, 103 different proteins were identified from 253 positive spot identifications. A bulk of cytoskeleton proteins such as actin, myosin light chains, and troponin were identified in the nuclear fraction, whereas mainly metabolic enzymes were detected in the cytosolic fraction. Transcription factors and proteins associated with protein biosynthesis were identified in skeletal muscles for the first time by proteomics. In addition, proteins involved in the mitochondrial redox system, as well as stress proteins, were identified. Results confirm the potential of this methodology to study the differential expressions of contractile proteins and metabolic enzymes, essential for generating functional diversity of muscles and muscle fiber types. Keywords Skeletal muscle; Subcellular fractionation; ProteomicsHuman skeletal muscle is very heterogeneous in composition, being constituted by different types of muscle fibers showing significant differences in their contractile speed and metabolic profile that result from specific protein expression [1][2][3][4]. In rodents, especially mice and rats, muscle fibers present a more uniform distribution among the different muscles, allowing the use of the entire muscles to study specific phenotypes. In this regard, the soleus and the white portion of gastrocnemius of mice are composed mainly of fast-and slow-twitch muscle fibers, respectively [5][6][7], and these two muscles have been used as typical models in proteomics. During the past few years, several studies have been performed using two-dimensional gel electrophoresis (2-DE) 1 combined with mass spectrometry (MS) to characterize skeletal muscle protein composition of typical slow-and fast-twitch skeletal muscles [8][9][10][11][12][13][14][15][16][17]. In a recent proteomics study on murine gastrocnemius and soleus muscle extracts, performed by Gelfi and coworkers [9], more than 800 spots on each 2-DE were detected by silver staining, leading to the identification of 85 different proteins belonging to the most abundant structural and metabolic protein classes. Despite the large number of visualized spots by 2-DE, proteins with lower relative abundances, usually involved in protein biosynthesis and cell stress response, are probably masked by structural or metabolic proteins [18,19]. To counteract this, Jarrold and coworkers [14] performed the depletion of abundant mus...

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Protein variants of skeletal muscle regulatory myosin light chain isoforms: prevalence in mammals, generation and transitions during muscle remodelling

Cited by 28 publications

References 38 publications

Proteomic profiling of chronic low‐frequency stimulated fast muscle

Proteomic profiling of chronic low‐frequency stimulated fast muscle

Drastic increase of myosin light chain MLC-2 in senescent skeletal muscle indicates fast-to-slow fibre transition in sarcopenia of old age

Subcellular proteomics of mice gastrocnemius and soleus muscles

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