domingo, abril 09, 2006

Biologia Molecular e Exercício

As tecnicas de Biologia Molecular tem sido utilizadas em grande escala por laboratótios de todo o mundo, com o objetivo de melhor entender a influência do treinamento físico sobre processos celulares de expressão gênica de proteínas e enzimas, ligadas ao metabolismo e a hipertrofia da célula muscular esquelética.
Estas descobertas tem dado novos rumos para a utilização e aplicação dos diferentes métodos de treinamento voltados a saúde e bem estar, desempenho e reabilitação.

Imagem obtida e adaptada de Google


Alguns estudos interesantes com foco na biologia molecular e treinamento físico tem seus resumos e links publicados abaixo:

Application of molecular biology in exercise physiology.

Booth FW.

Past progress in exercise biochemical research has often depended on the use of knowledge and techniques which were originally reported from other disciplines. With the advent of newer methodologies in molecular biology, the purpose of this review has been to document the status of information gained from the application of molecular biological techniques to questions in exercise physiology. Furthermore, this review has speculated how new methods in molecular biology might be employed to answer classic questions in exercise physiology. A powerful revolution in science, that is, molecular biology, will provide new information about exercise mechanisms, which ideally will improve the training programs for elite athletes as well as continue to be associated with the public's interest in exercise training.


Transcriptional regulation in response to exercise.

Baar K, Blough E, Dineen B, Esser K.

Graduate Program, School of Kinesology, College of Health and Human Development Sciences, Chicago, Illinois, USA.

Much progress has been made in recent years into understanding molecular mechanisms by which transcription is regulated following changes in physiological stimuli. This review has tried to focus on what is known about four specific physiological challenges--mechanical load, intracellular calcium, hypoxia, and redox state. Because of our biased interest in exercise, it was our goal to review these relatively well-studied systems so that we might provide insight into potential mechanisms that govern exercise-induced transcriptional changes. What becomes obvious, when reaching the end of this review, is that there are many common themes among the different physiological responses described. Some examples include the activation of IEGs, such as c-jun and c-fos, the phosphorylation of the transcription factor CREB, and the importance of the serum response element and the serum response factor. These commonalities across the different physiological systems suggest a certain redundancy or shared mechanism(s) for regulating transcription in response to physiological stimuli. While very little is known at this time about how exercise regulates transcription, it is an exciting time in this field of research. The recent growth in the molecular biological research literature of more physiologically-based studies provides exciting new molecular and cellular tools for those researchers willing to take on the challenge of understanding the complex mechanisms of exercise-induced adaptations.


Adaptations of skeletal muscle to exercise: rapid increase in the transcriptional coactivator PGC-1.

Baar K, Wende AR, Jones TE, Marison M, Nolte LA, Chen M, Kelly DP, Holloszy JO.

Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110, USA.

Endurance exercise induces increases in mitochondria and the GLUT4 isoform of the glucose transporter in muscle. Although little is known about the mechanisms underlying these adaptations, new information has accumulated regarding how mitochondrial biogenesis and GLUT4 expression are regulated. This includes the findings that the transcriptional coactivator PGC-1 promotes mitochondrial biogenesis and that NRF-1 and NRF-2 act as transcriptional activators of genes encoding mitochondrial enzymes. We tested the hypothesis that increases in PGC-1, NRF-1, and NRF-2 are involved in the initial adaptive response of muscle to exercise. Five daily bouts of swimming induced increases in mitochondrial enzymes and GLUT4 in skeletal muscle in rats. One exercise bout resulted in approximately twofold increases in full-length muscle PGC-1 mRNA and PGC-1 protein, which were evident 18 h after exercise. A smaller form of PGC-1 increased after exercise. The exercise induced increases in muscle NRF-1 and NRF-2 that were evident 12 to 18 h after one exercise bout. These findings suggest that increases in PGC-1, NRF-1, and NRF-2 represent key regulatory components of the stimulation of mitochondrial biogenesis by exercise and that PGC-1 mediates the coordinated increases in GLUT4 and mitochondria.


Involvement of PPAR gamma co-activator-1, nuclear respiratory factors 1 and 2, and PPAR alpha in the adaptive response to endurance exercise.
Baar K.

Department of Mechanical Engineering and Institute of Gerontology, University of Michigan, Ann Arbor, MI 48109-2007, USA. kbaar@umich.edu

Endurance exercise training induces an increase in the respiratory capacity of muscle, resulting in an increased capacity to generate ATP as well as improved efficiency of muscle contraction. Such adaptations are largely the result of a coordinated genetic response that increases mitochondrial proteins, fatty acid oxidation enzymes and the exercise- and insulin-stimulated glucose transporter GLUT4, and shifts the contractile and regulatory proteins to their more efficient isoforms. In recent years a number of the transcriptional regulators involved in this genetic response have been identified and these factors can be classified into two different groups. The first group comprises transcription factors such as nuclear respiratory factors (NRF) 1 and 2 and PPAR alpha that bind DNA in a sequence-specific manner. The second group, referred to as transcriptional co-activators, alter transcription without directly binding to DNA. The PPAR gamma co-activator (PGC) family of proteins have been identified as the central family of transcriptional co-activators for induction of mitochondrial biogenesis. PGC-1 alpha is activated by exercise, and is sufficient to produce the endurance phenotype through direct interactions with NRF-1 and PPAR alpha, and potentially NRF-2. Furthering the understanding of the activation of PGC proteins following exercise has implications beyond improving athletic performance, including the possibility of providing targets for the treatment of frailty in the elderly, obesity and diseases such as mitochondrial myopathies and diabetes.

Mechanical signals, IGF-I gene splicing, and muscle adaptation.
Goldspink G.

Basic Division of Basic Medical Sciences and Department of Surgery, Royal Free and University College Medical School, London, UK. goldspink@medsch.ucl.ac.uk

Combining physiological and molecular biology methods made it possible to identify and characterize a local muscle growth/repair factor (MGF). Following resistance exercise, MGF "kick starts" muscle hypertrophy and is important in local tissue repair. Loss of muscle mass in old age and certain diseases is associated with an impaired ability to express MGF.

Diet, genes and exercise performance.
Hargreaves M.

Centre for Physical Activity and Nutrition Research, School of Health Sciences, Deakin University, Burwood, VIC 3125.

The importance of nutrition, in combination with appropriate training, for successful exercise performance has been recognised for many years. Considerable emphasis has rightly focused on energy, carbohydrate and fluid balance, and nutritional strategies are designed to prevent the well documented ergolytic effects of carbohydrate depletion and dehydration on endurance exercise performance. In addition, attention has focused on the role on nutrition in promoting optimal biological adaptations to training, again with an emphasis on carbohydrate and fluid balance, but with emerging interest in the role of protein intake. In recent years, advances in molecular biology techniques have allowed investigation of the effects of exercise and diet on skeletal muscle gene expression and of the importance of the genotype in determining the biological responses to exercise and dietary interventions. It is clear that a number of putative genes have associations with cardiorespiratory endurance, muscle strength and metabolism, specific characteristics of elite athletes and with training adaptability. A challenge in the years ahead is to assess the relative importance of the genotype and the environment in determining the final "elite performance phenotype". A relatively simpler task has been examination of the effects of exercise and dietary intervention on gene expression in human skeletal muscle. A single bout of exercise increases the rate of transcription and the mRNA levels of a number of metabolic genes during and after exercise. The increases are most marked during recovery from exercise and are transient, suggesting that the long term effects of exercise training may be the result of ongoing and repeated increases in mRNA, ultimately leading to steady-state increases in expression of key proteins involved in energy metabolism. Cessation of training results in a rapid reversal of many adaptive responses. Interestingly, recent results suggest that the increases in gene transcription may be influenced by the preceding diet, most notably the availability of muscle glycogen and blood glucose (Hargreaves et al., unpublished). We have also observed that short-term manipulation of dietary carbohydrate and fat intake modifies the expression of genes within muscles of athletes maintaining their normal training. Our recent observation of nuclear translocation of AMP-activated protein kinase during exercise provides a potential mechanism linking metabolic events within contracting muscle to gene transcription.

Molecular and genetic approaches to studying exercise performance and adaptation.
Allen DL, Harrison BC, Leinwand LA.

Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder 80309, USA.

The increasing availability of molecular biological techniques has allowed exercise researchers to examine the molecular mechanisms underlying exercise performance and adaptation. We discuss three molecular approaches that can evaluate the role of individual genes in the exercise response, and could provide a foundation for more effective exercise regimens for humans.



What makes an endurance athlete world-class? Not simply a physiological conundrum.

Myburgh KH.

Department of Physiological Sciences, University of Stellenbosch, Stellenbosch, Private Bag X1, 7602, Matieland, South Africa. khm@sun.ac.za

Inter-individual variation in endurance performance capacity is a characteristic, not only of the general population, but also in trained athletes. The ability of sport scientists to predict which athletes amongst an elite group will become world-class is limited. We do not fully understand the interactions between biological factors, training, recovery and competitive performance. Assessment methods and interpretation of results do not take into account the facts that most research is not done on elite athletes and performances of world-class endurance athletes cannot be attributed to aerobic capacity alone. Many lines of evidence suggest that there is a limit to adaptation in aerobic capacity. Recent advances in molecular biology and genetics should be harnessed by exercise biologists in conjunction with previously used physiological, histological and biochemical techniques to study elite athletes and their responses to different training and recovery regimens. Technological advances should be harnessed to study world-class athletes to determine optimal training and competition strategies. In summary, it is likely that multiple factors are essential contributors to world-class endurance performance and that it is only by using a multidisciplinary approach that we will come closer to solving the conundrum: 'What makes an endurance athlete world class?'

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