Regulation of Protein Synthesis: Singular and Combined Effects of Age, AMPK, and Resisted Contractions on Control of Protein Synthesis and Elongation Factors in Skeletal Muscle PDF Download
Are you looking for read ebook online? Search for your book and save it on your Kindle device, PC, phones or tablets. Download Regulation of Protein Synthesis: Singular and Combined Effects of Age, AMPK, and Resisted Contractions on Control of Protein Synthesis and Elongation Factors in Skeletal Muscle PDF full book. Access full book title Regulation of Protein Synthesis: Singular and Combined Effects of Age, AMPK, and Resisted Contractions on Control of Protein Synthesis and Elongation Factors in Skeletal Muscle by Christopher Alan Fick. Download full books in PDF and EPUB format.
Author: Christopher Alan Fick
Publisher:
ISBN: 9781109935875
Category : Muscles
Languages : en
Pages : 92
Get Book Here
Book Description
The age-related decline in muscle mass (sarcopenia) can be attenuated but not completely prevented by resistance exercise. This phenomenon may be attributable in part to diminished overload-induced protein synthesis rates in aged skeletal muscle. While the mechanisms underlying this effect are unclear, potential contributing factors may include age-related differences in the activation of translational signaling through the mammalian target of rapamycin (mTOR) and its direct and indirect downstream targets including the 70-kDa ribosomal protein S6 kinase (p70S6k) and eukaryotic elongation factor-2 (eEF2). Translational signaling is rapidly but transiently elevated following resistance exercise, while protein synthesis rates are not elevated until several hours later. It has been postulated that this early event may therefore be an important priming step for the protein synthesis response, but this hypothesis had not previously been tested. Thus, we first explored this possibility in young adult (Y; 8mo.) male Fischer344 x Brown Norway (FBN) rats by inhibiting early post-resistance exercise [achieved via high frequency electrical stimulation (HFES)] translational signaling via pharmacological activation of 5'-AMP-activated protein kinase (AMPK, a known inhibitor of translational signaling and protein synthesis) with 5-aminoimidazole-4-carboxamide-1-4-ribofuranoside (AICAR). As hypothesized, this inhibition prevented the exercise-associated increase in protein synthesis rate seen 24 hours later in saline-treated control animals. In a second experiment, in vivo AMPK activity was elevated in skeletal muscle of old (O; 30mo.) but not of Y FBN rats following HFES in both lengthening and shortening skeletal muscle. However, in contrast to the findings with pharmacological AMPK activation, the physiological AMPK response to resistance exercise in O skeletal muscle did not consistently coincide with an apparent inhibitory effect on early post-exercise translational signaling. Interestingly, the protein synthesis response at 24 hours was attenuated with age, but for reasons currently unclear, this only occurred in shortening but not in lengthening skeletal muscle. Taken together, these results suggest that the early post-resistance exercise elevation in translational signaling may be necessary for the sustained increase in protein synthesis rate seen 24 hours later. However, the normal physiological AMPK response to this HFES protocol in O animals was not consistently associated with discernibly less translational signaling or protein synthesis rates vs. their Y counterparts.
Author: Christopher Alan Fick
Publisher:
ISBN: 9781109935875
Category : Muscles
Languages : en
Pages : 92
Get Book Here
Book Description
The age-related decline in muscle mass (sarcopenia) can be attenuated but not completely prevented by resistance exercise. This phenomenon may be attributable in part to diminished overload-induced protein synthesis rates in aged skeletal muscle. While the mechanisms underlying this effect are unclear, potential contributing factors may include age-related differences in the activation of translational signaling through the mammalian target of rapamycin (mTOR) and its direct and indirect downstream targets including the 70-kDa ribosomal protein S6 kinase (p70S6k) and eukaryotic elongation factor-2 (eEF2). Translational signaling is rapidly but transiently elevated following resistance exercise, while protein synthesis rates are not elevated until several hours later. It has been postulated that this early event may therefore be an important priming step for the protein synthesis response, but this hypothesis had not previously been tested. Thus, we first explored this possibility in young adult (Y; 8mo.) male Fischer344 x Brown Norway (FBN) rats by inhibiting early post-resistance exercise [achieved via high frequency electrical stimulation (HFES)] translational signaling via pharmacological activation of 5'-AMP-activated protein kinase (AMPK, a known inhibitor of translational signaling and protein synthesis) with 5-aminoimidazole-4-carboxamide-1-4-ribofuranoside (AICAR). As hypothesized, this inhibition prevented the exercise-associated increase in protein synthesis rate seen 24 hours later in saline-treated control animals. In a second experiment, in vivo AMPK activity was elevated in skeletal muscle of old (O; 30mo.) but not of Y FBN rats following HFES in both lengthening and shortening skeletal muscle. However, in contrast to the findings with pharmacological AMPK activation, the physiological AMPK response to resistance exercise in O skeletal muscle did not consistently coincide with an apparent inhibitory effect on early post-exercise translational signaling. Interestingly, the protein synthesis response at 24 hours was attenuated with age, but for reasons currently unclear, this only occurred in shortening but not in lengthening skeletal muscle. Taken together, these results suggest that the early post-resistance exercise elevation in translational signaling may be necessary for the sustained increase in protein synthesis rate seen 24 hours later. However, the normal physiological AMPK response to this HFES protocol in O animals was not consistently associated with discernibly less translational signaling or protein synthesis rates vs. their Y counterparts.
Author:
Publisher:
ISBN: 9789175495132
Category :
Languages : en
Pages : 67
Get Book Here
Book Description
Author: Jennifer Macesich
Publisher:
ISBN:
Category : Adenylic acid
Languages : en
Pages : 115
Get Book Here
Book Description
Sarcopenia is associated with an age-related decrease in skeletal muscle mass, which can result in decreases in strength and physical functioning in the older population. Resistance training interventions are not completely effective in stimulating muscle protein synthesis in aged muscle and thus do not completely combat age-related atrophy. Phosphorylation (and thus theoretically activation) of the energy-sensing molecule 5'-AMP-activated protein kinase (AMPK, known to inhibit the muscle protein synthesis pathway) has been shown to be elevated for up to three hours in response to a resistance training bout in the muscles of older, but not younger individuals. Data in rats indicate that, in response to muscle contractions, elevated AMPK activity can accentuate the inhibitory phosphorylation (and thus deactivation) of its downstream intermediate, eukaryotic elongation factor 2 (eEF2, which normally stimulates protein translation and synthesis). AMPK activity is inhibited by high muscle glycogen levels. Interestingly, older individuals exhibit a lower muscle glycogen content compared to younger individuals, which may account for the greater AMPK phosphorylation response to resistance exercise in older individuals. The relationship between muscle glycogen content, AMPK activity, and eEF2 phosphorylation in response to an acute bout of resistance exercise has not yet been examined in young or old individuals. We hypothesized that inhibitory eEF2 phosphorylation would be higher in response to an acute resistance exercise bout in the skeletal muscles of older versus younger individuals. We further hypothesized that this higher eEF2 phosphorylation response would be related to a higher AMPK activation, and that higher AMPK activation would be related to lower glycogen content, in the skeletal muscles of older versus younger individuals. Seven young (21.7 " 0.8 yrs) and 10 old (67.0 " 2.6 yrs) untrained but physically active men and women performed 3 sets of leg extensions at a 10-repetition maximum resistance until failure after an overnight fast. Muscle biopsies were obtained from the vastus lateralis pre-exercise (PRE), immediately post exercise (0P), 1-hour post exercise (1P), and 2-hours post exercise (2P). Glycogen content was measured in muscle samples, as were the phosphorylations, by western blot, of AMPK (Thr172), acetyl-CoA carboxylase (ACC, a marker of in vivo AMPK activity) (Ser79), and eEF2 (Thr56). Muscle glycogen content was significantly lower in the old vs. young subjects at the PRE time point and decreased in response to exercise in both age groups; however, glycogen content decreased to a greater degree in young subjects such that it was equal between young and old at all post-exercise timepoints. As expected, AMPK phosphorylation was significantly increased in the old subjects immediately post exercise, but no such response was noted in the young. However, no age-related differences were observed in AMPK activity as measured by ACC phosphorylation, which was significantly elevated at 0P and 1P in both age groups. Similarly, the eEF2 phosphorylation response (elevated vs. PRE at 0P and decreased vs. PRE at 1P and 2P in both age groups) was also not affected by age. Regardless of age, higher muscle glycogen content was associated with lower AMPK activity (as assessed by phospho-ACC content) at 0P and 1P, and this lower AMPK activity was associated with lower inhibitory phosphorylation of eEF2 at those same timepoints. These findings indicate the possibility that higher muscle glycogen content may result in lower AMPK activation and consequently lower inhibitory eEF2 phosphorylation in response to a resistance training session in the muscles of both younger and older individuals, thereby potentially enabling greater translation elongation, protein synthesis, and muscle growth regardless of age.
Author:
Publisher:
ISBN:
Category : Dissertations, Academic
Languages : en
Pages : 1044
Get Book Here
Book Description
Author: Paige Chandler
Publisher:
ISBN:
Category :
Languages : en
Pages :
Get Book Here
Book Description
Muscle growth is advantageous not only because of its roles in mobility and breathing, but because increases in muscle mass increase physical strength, reduces the risk of injury, increases bone strength, and promotes immune function. Given the various roles of skeletal muscle, it is clear that inadequately maintaining muscle mass and function is a threat to an individuals quality of life and health.Muscle atrophy is a debilitating condition that commonly occurs in conjunction with disuse due to injury, aging, and chronic illness. In 2012, more than 54% of US adults suffered from a musculoskeletal disorder (MSDs), the vast majority of which are caused by traumatic illness. As a result, MSDs represent the second highest cause of disability. As for the aging population, the US Census Bureau has predicted that 20% (80 million) of the population will be > 65 years of age by 2050. The economic burden of age-related muscle loss is so great that a 10% reduction in age-related muscle loss would save the US $1 billion in health costs per year. Finally, 60% of US adults are living with one chronic illness while 42% are living with two. Given the alarming incidence of conditions which promote muscle atrophy, it is imperative to fully understand the biological underpinnings of muscle growth. Skeletal muscle hypertrophy occurs when rates of protein synthesis exceed rates of protein degradation. Most studies centered on the regulation of muscle mass emphasize the role of protein synthesis while there is less emphasis placed on the role of protein degradation. However, protein degradation is required for the quick and efficient removal of not only damaged proteins, but ~20% of the cellular proteome. Indeed, the ubiquitin-proteasome system (UPS), one of the predominant proteolytic systems in muscle, controls the expression of regulatory factors like cell cycle proteins, transcription factors, and signaling molecules. This means that the UPS can selectively control gene expression, and signal transduction. Unfortunately, because one of the hallmarks of muscle atrophy is hyperactive proteolysis by the UPS, proteolysis generally has a negative connotation in muscle. Nonetheless, the UPS is necessary for muscle hypertrophy because inhibition of the UPS in various rodent and human models causes defects in muscle growth, architecture, and function. Therefore, we propose that the UPS is crucially involved in skeletal muscle growth. The goal of my dissertation research was to identify a precise role for the UPS during hypertrophy. We hypothesized that UPS inhibition would impair growth by blocking ribosomal DNA (rDNA) transcription and ribosome production. In order to study the role of the proteasome in skeletal muscle growth, we used the reversible but potent 26S proteasome inhibitor MG-132. We found that inhibition of the proteasome, but not other prominent proteolytic systems, blocked hypertrophy by impairing rDNA transcription and ribosome production. We further hypothesized that proteasome inhibition would lead to the accumulation of p53, a negative regulatory factor of rDNA transcription. Indeed, p53 accumulated upon proteasome inhibition, which impaired rDNA transcription by reducing RNA Pol I recruitment to the rDNA promoter. Collectively, my dissertation work highlights the role of the UPS in the transcriptional regulation of muscle hypertrophy. Specifically, this work demonstrates that the UPS is not a passive participant in growth but has precise molecular roles in the regulation of muscle mass. Furthermore, this study is important for the development of therapeutics for those individuals suffering from chronic muscle loss. We can conclude that inhibition of the UPS may not be the best target for those individuals suffering from muscle atrophy as UPS inhibition might exacerbate muscle loss.
Author: Mark Hargreaves
Publisher: Human Kinetics
ISBN: 9780736041034
Category : Energy metabolism
Languages : en
Pages : 320
Get Book Here
Book Description
A comprehensive reference for biochemists, sport nutritionists, exercise physiologists, and graduate students in those disciplines. Provides information on the metabolic processes that take place during exercise, examining in depth the mobilization and utilization of substrates during physical activity. Focuses primarily on the skeletal muscle, but also discusses the roles of the liver and adipose tissue. Annotation copyright by Book News, Inc., Portland, OR
Author: Alfred Wittinghofer
Publisher: Springer
ISBN: 3709118069
Category : Science
Languages : en
Pages : 447
Get Book Here
Book Description
This first of two volumes provides a general overview of the genetics, structure, mechanism and regulation of the Ras superfamily proteins and describes in detail the signaling pathways and processes regulated by specific members of this family. The focus of this first volume is on the Rho and Ras subfamily of small G proteins. Renowned scientists provide insights into the biochemistry of the classical and non-classical small G-protein family members, their spatio-temporal regulation, their effectors and their roles in health and disease. Together with Volume 2, this book provides a comprehensive and state-of-the-art work on small G-proteins (GTPases). It is intended for graduates and professors in biochemistry and cell biology already working on small G-proteins (small GTPases), but also offers an extremely valuable resource for those readers who are new to the field.
Author: AnnMarie Kocher
Publisher: Springer Science & Business Media
ISBN: 1607616165
Category : Medical
Languages : en
Pages : 318
Get Book Here
Book Description
Nitrite and Nitrate in Human Health and Disease delivers a comprehensive review of nitrite and nitrate biology, from basic biochemistry to the complex physiology and metabolism of these two naturally occurring molecules in the human body. Well-organized and well referenced chapters cover the rich history of nitrite and nitrate, sources of exposure, and the physiological effects when consumed through foods containing nitrite and nitrate. The chapters are written by leading experts, all of whom share their research and perspectives in order to help define the context for benefits vs. any potential risks associated with nitrite and nitrate use, either through dietary ingestion or therapeutic dosing. This diverse collection of authors includes vascular biologists, physiologists, physicians, epidemiologists, cancer biologists, registered dieticians, chemists, and public health experts from five countries in both academia and government. Nitrite and Nitrate in Human Health and Disease provides a balanced view of nitric oxide biochemistry, and nitrite and nitrate biochemistry in physiology and in the food sciences.
Author: Pragya Mishra
Publisher: Springer Nature
ISBN: 9811561214
Category : Medical
Languages : en
Pages : 522
Get Book Here
Book Description
This book gathers a collection of essays that describe recent innovations in food technology including food processing, packaging, food safety, and novel ingredients. By 2050, the world will face the challenge of having to feed an estimated 9 billion people. In order to meet that challenge, innovations in food research are of the utmost importance. The book is divided into four sections, each of which explores an important aspect like food processing, food microbiology, and nutritional security. Written by respected scholars in the field, the respective chapters discuss a range of new and enhanced food materials, as well as processing innovations to extend shelf life and reduce toxic effects. The book also addresses the health potential of various nutraceuticals, bio-absorption of metals and their positive impacts on living systems, as well as methods for reducing food wastage, preventing the loss of nutritive value, and preserving or enhancing palatability. Given its scope, the book will be highly interesting for food scientists, both in academia and the food industry. It will also benefit advanced graduate students and senior researchers.
Author: Joshua A. Zeichner
Publisher: Springer Science & Business Media
ISBN: 1461483441
Category : Medical
Languages : en
Pages : 405
Get Book Here
Book Description
Dermatologists commonly treat acne, which affects 40 to 50 million Americans each year and about 85 percent of all patients at some point in their lives. Dermatologists, primary care doctors, and pediatricians see these patients every day in practice. It is important to treat the skin effectively not only to reduce the risk of physical scarring, but also to address the negative psychosocial impact this disease carries. Improving the skin can improve self-confidence, interpersonal relationships, and performance in school or at work. Acneiform Eruptions in Dermatology is a practical, full-color guide to the differential diagnosis of acne vulgaris and the treatment of acne-like conditions. It is organized into sections by subtype of condition (e.g., infections, genetic syndromes, medication-caused) and includes a section of variants of acne that may be misdiagnosed. Within the sections, individual chapters discuss each variant of the condition and begin with a helpful bulleted summary of its defining clinical features. Extensive color clinical images appear throughout the book.
