Characterization of a rabbit antihuman mechano growth factor (MGF) polyclonal antibody against the last 24 amino acids of the E domain (original) (raw)
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Journal of Applied Physiology, 2010
Insulin-like growth factor I (IGF-I) coordinates proliferation and differentiation in a wide variety of cell types. The igf1 gene not only produces IGF-I, but also generates multiple carboxy-terminal extensions, the E-peptides, through alternative splicing leading to different isoforms. It is not known if the IGF-I isoforms share a common pathway for their actions, or if there are specific actions of each protein. Viral administration of murine IGF-IA, IGF-IB, and mature IGF, which lacked an E-peptide extension, was utilized to identify IGF-I isoform specific responsive genes in muscles of young growing mice.
The Journal of Physiology, 2003
Insulin-like growth factor-I (IGF-I) has several important physiological functions, particularly during growth and development. Recently, it has become apparent that IGF-I exists in different isoforms and that several tissues produce IGF-I for autocrine and paracrine actions (Stewart & Rotwein, 1996). At least two isoforms of the IGF-I gene have recently been shown to be expressed by animal muscles when subjected to mechanical stimulation (Yang et al. 1996; McKoy et al. 1999). The role of these isoforms and the physiological and molecular mechanisms that regulate their expression is unclear and very little is known about their expression in human skeletal muscle. An isoform of IGF-I (IGF-IEa) in muscle is similar to the hepatic endocrine type of IGF-I. Increasing the expression of this isoform by injection of a plasmid or a viral construct (Barton-Davies et al. 1998) containing the IGF-IEa cDNA into a mouse muscle has been shown to produce an anabolic effect. This resulted in an average increase of 15 % in muscle mass and the prevention of age-related loss of muscle mass (sarcopenia) in old mice. The role of this isoform as a potential hypertrophic agent was further supported in a recent study in which a transgenic mouse model, that overexpressed this isoform in skeletal muscle, was shown to have pronounced muscle hypertrophy (Musaro et al. 2001).
American Journal of Physiology-Endocrinology and Metabolism, 2013
A splice form of IGF-1, IGF-1Eb, is upregulated after exercise or injury. Physiological responses have been ascribed to the 24-amino acid COOH-terminal peptide that is cleaved from the NH3-terminal 70-amino acid mature IGF-1 protein. This COOH-terminal peptide was termed “mechano-growth factor” (MGF). Activities claimed for the MGF peptide included enhancing muscle satellite cell proliferation and delaying myoblast fusion. As such, MGF could represent a promising strategy to improve muscle regeneration. Thus, at our two pharmaceutical companies, we attempted to reproduce the claimed effect of MGF peptides on human and mouse muscle myoblast proliferation and differentiation in vitro. Concentrations of peptide up to 500 ng/ml failed to increase the proliferation of C2C12 cells or primary human skeletal muscle myoblasts. In contrast, all cell types exhibited a proliferative response to mature IGF-1 or full-length IGF-1Eb. MGF also failed to inhibit the differentiation of myoblasts into...
The role of the insulin-like growth factor 1 (IGF-1) in skeletal muscle physiology
2007
Abstract The human insulin-like growth factor-1 (IGF-1) gene gives rise to multiple, heterogeneous mRNA transcripts through a combination of multiple transcription initiation sites, alternative splicing and different polyadenylation signals. These IGF-1 mRNA transcripts code different isoforms of the precursor peptide of IGF-1 (IGF-1Ea, IGF-1Eb and IGF-1Ec or MGF in human skeletal muscle), which also undergo post-translational modification.
Objective: Insulin-like growth factor-1 (IGF-1) is a pleiotropic factor expressed in various tissues and plays a critical role in skeletal muscle physiology. Alternative splicing of the IGF-1 gene gives rise to different precursor polypep-tides (isoforms) which could undergo post-translational cleavage, generating the common mature IGF-1 peptide and different carboxyl terminal extension (E-) peptides, with the fate of the latter being, so far, unknown. The objective if this study was to identify the IGF-1Ec forms or processing product(s), other than mature IGF-1, generated in different human and rodent tissues and particularly in human skeletal muscle after exercise-induced damage. Design: Protein lysates from a wide range of human and rodent tissues were immunoblotted with a rabbit anti-human Ec polyclonal antibody raised against the last 24 amino acids of the C-terminal of the Ec peptide. This anti-body can recognize the Ec peptide, both as part of IGF-1Ec and alone, and also the corresponding rodent forms, due to the high homology that the human Ec shares with the rodent Eb. Results: We were able to confirm, for the first time, that the human Ec peptide and its rodent homologous Eb peptide are produced simultaneously with their precursor protein (pro-IGF-1Ec/Eb) in vivo, in a wide range of tissues (e.g. muscle, liver, heart). Proprotein convertase furin digestion of human muscle and liver protein lysates confirmed that the higher molecular form, pro-IGF-1Ec, can be cleaved to produce the free Ec peptide. Furthermore, initial evidence is provided that Ec peptide is differentially regulated during the process of muscle regeneration after exercise-induced damage in humans. Conclusions: The findings of this study possibly imply that the post-translational modification of the IGF-1Ec pro-peptide may regulate the bioavailability and activity of the processing product(s).
2016
Purpose: The human insulin-like growth factor-1 (IGF-1) is a peptide believed to play an important role in the regulation of cellular growth and differentiation. The aim of the present study was to investigate the responses of IGF-1Ea and mechanogrowth factor (MGF) to two different training methods. Materials and Methods: To this end, fourteenphysically active male subjects were randomly divided into two groups: plyometric training (n=7, group A)whose subjects were trained with plyometric training and combined training (n=7, group B)whose subjects were trained with traditional resistance training combined with plyometric training, 3 days aweek for 8 weeks.Muscle biopsies were obtained from VastusLateralismuscle 3 days before and 7 days after training. To evaluate muscle strength and power, agility and speed, back squat, continuous jump (5 minutesand 60 seconds), vertical jump,standing long jump, Hexagonal Obstacle, and 35m dash tests were used, respectively. For estimating gene expr...
Reconciling data from transgenic mice that overexpress IGF-I specifically in skeletal muscle
Growth Hormone & IGF Research, 2005
Transgenic mice that overexpress insulin-like growth factor-1 (IGF-I) specifically in skeletal muscle have generated much information about the role of this factor for muscle growth and remodelling and provide insight for therapeutic applications of IGF-I for different pathological states and ageing. However, difficulties arise when attempting to critically compare the significance of data obtained in vivo by using different genetically engineered mouse lines and various experimental models. Complications arise due to complexity of the IGF-I system, since multiple transcripts of the IGF-I gene encode different isoforms generated by alternate promoter usage, differential splicing and post-translational modification, and how IGF-I gene expression relates to its diverse autocrine, paracrine and endocrine modes of action in vivo has still to be elucidated. In addition, there are problems related to specification of the exact IGF-I isoform used, expression patterns of the promoters, and availability of the transgene product under different experimental conditions. This review discusses the factors that must be considered when reconciling data from cumulative studies on IGF-I in striated muscle growth and differentiation using genetically modified mice. Critical evaluation of the literature focuses specifically on: (1) the importance of detailed information about the IGF-I isoforms and their mode of action (local, systemic or both); (2) expression pattern and strength of the promoters used to drive transgenic IGF-I in skeletal muscle cells (mono and multi-nucleated); (3) local compared with systemic action of the transgene product and possible indirect effects of transgenic IGF-I due to upregulation of other genes within skeletal muscle; (4) re-interpretation of these results in light of the most recent approaches to the dissection of IGF-I function. Full understanding of these complex in vivo issues is essential, not only for skeletal muscle but for many other tissues, in order to effectively extend observations derived from transgenic studies into potential clinical situations.
Insulin-like growth factors (IGF1, IGF2) are part of the somatotropic axis – a group of substances involved in controlling many important functions, including muscle growth of mammalian organism. In the study, we analysed changes in the expression level of IGFs in muscles during development of pigs (between 60 and 210 days of age). We also compared expression level of IGFs between groups of pigs representing five breeds differing in productive traits. Expression level of IGF2 gene decreased significantly (max. 9-fold) with aging of the animals. Level of IGF1 also declined but only slightly. Between breed analysis confirmed the effect of IGF2 G3072A SNP on expression level and indicated the presence of an additional factor influencing expression of IGF2 gene. Moreover, we observed overexpression of IGF1 gene in the Pietrain breed at some developmental stages.