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Mechanical perturbation triggers activation of resident myogenic stem cells to enter the cell cycle through a cascade of events including hepatocyte growth factor (HGF) release from its extracellular tethering and the subsequent presentation to signaling‐receptor c‐met. Here, we show that with aging, extracellular HGF undergoes tyrosine‐residue (Y) nitration and loses c‐met binding, thereby disturbing muscle homeostasis. Biochemical studies demonstrated that nitration/dysfunction is specific to HGF among other major growth factors and is characterized by its locations at Y198 and Y250 in c‐met‐binding domains. Direct‐immunofluorescence microscopy of lower hind limb muscles from three age groups of rat, provided direct in vivo evidence for age‐related increases in nitration of ECM‐bound HGF, preferentially stained for anti‐nitrated Y198 and Y250‐HGF mAbs (raised in‐house) in fast IIa and IIx myofibers. Overall, findings highlight inhibitory impacts of HGF nitration on myogenic stem cell dynamics, pioneering a cogent discussion for better understanding age‐related muscle atrophy and impaired regeneration with fibrosis (including sarcopenia and frailty). [ABSTRACT FROM AUTHOR]

This document is the cover legend for an article titled "Age-related nitration/dysfunction of myogenic stem cell activator HGF" published in the journal Aging Cell. The article, authored by Alaa Elgaabari et al., explores the impact of aging on the function of a protein called HGF, which is involved in the activation of stem cells responsible for muscle regeneration. The research suggests that age-related nitration of HGF may contribute to the decline in muscle regeneration observed in older individuals. The article includes a list of all the authors involved in the study. [Extracted from the article]

In response to peroxynitrite (ONOO−) generation, myogenic stem satellite cell activator HGF (hepatocyte growth factor) undergoes nitration of tyrosine residues (Y198 and Y250) predominantly on fast IIa and IIx myofibers to lose its binding to the signaling receptor c‐met, thereby disturbing muscle homeostasis during aging. Here we show that rat anti‐HGF monoclonal antibody (mAb) 1H41C10, which was raised in‐house against a synthetic peptide FTSNPEVRnitroY198EV, a site well‐conserved in mammals, functions to confer resistance to nitration dysfunction on HGF. 1H41C10 was characterized by recognizing both nitrated and non‐nitrated HGF with different affinities as revealed by Western blotting, indicating that the paratope of 1H41C10 may bind to the immediate vicinity of Y198. Subsequent experiments showed that 1H41C10‐bound HGF resists peroxynitrite‐induced nitration of Y198. A companion mAb‐1H42F4 presented similar immuno‐reactivity, but did not protect Y198 nitration, and thus served as the control. Importantly, 1H41C10‐HGF also withstood Y250 nitration to retain c‐met binding and satellite cell activation functions in culture. The Fab region of 1H41C10 exerts resistivity to Y250 nitration possibly due to its localization in the immediate vicinity to Y250, as supported by an additional set of experiments showing that the 1H41C10‐Fab confers Y250‐nitration resistance which the Fc segment does not. Findings highlight the in vitro preventive impact of 1H41C10 on HGF nitration‐dysfunction that strongly impairs myogenic stem cell dynamics, potentially pioneering cogent strategies for counteracting or treating age‐related muscle atrophy with fibrosis (including sarcopenia and frailty) and the therapeutic application of investigational HGF drugs. [ABSTRACT FROM AUTHOR]

To clarify the relationship between the fiber type composition and meat quality, we performed metabolomic analysis using porcine longissimus dorsi (LD) muscles. In the LD of pigs raised outdoors, the expression of myosin heavy chain (MyHC)1 (slow-twitch fiber marker protein) was significantly increased compared with that of MyHC1 in pigs raised in an indoor pen, suggesting that rearing outdoors could be considered as an exercise treatment. These LD samples were subjected to metabolomic analysis for examining the profile of most primary and secondary metabolites. We found that the sex of the animal and exercise stimulation had a strong influence on the metabolomic profile in the porcine skeletal muscles, and this difference in the metabolomic profile is likely in part due to the changes in the muscle fiber type. We also examined the effects of cooking (70 °C for 1 h). The effect of exercise on the metabolomic profile was also maintained in the cooked muscle tissues. Cooking treatment resulted in an increase in some of the metabolite levels while decreasing in some other metabolite levels. Thus, our study could indicate the effect of the sex of the animal, exercise stimulus, and cooking on the metabolomic profile of pork meat. [ABSTRACT FROM AUTHOR]

The contractile and metabolic properties of skeletal muscles depend on the composition of muscle fibers. There are two major fiber types: type 1 and type 2. Type 2 fibers are further subdivided into type 2A, 2X, and 2B fibers. Muscle fiber type composition is an important property that affects sports performance and metabolic ability in humans, and meat quality in domestic animals. In this review, we summarize the history of muscle fiber type classification based on various staining methods for skeletal muscle sections. The history illustrates the development of an experimental method to detect myosin heavy chain (MyHC) proteins, which are the most common marker molecules for muscle fiber type. Metabolic enzymes, such as nicotinamide adenine dinucleotide-tetrazolium reductase and succinate dehydrogenase are also described for histochemical staining combined with myosin ATPase staining. We found an improvement in the quality of antibodies used for immunostaining of MyHC, from polyclonal antibodies to monoclonal antibodies (mAbs) and then to mAbs produced by synthetic peptides as antigens. We believe that the information presented herein will assist researchers in selecting optimal staining methods, dependent on the experimental conditions and purposes.