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Exercise Tames the Wild-side of The Myc-network: A Hypothesis.
MedLine Citation:
PMID:  22535747     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Pleiotropic, beneficial effects of regular physical activity are well documented. Diverse molecular and cellular networks have been identified as contributors to the health benefits of regular exercise. However, none of those networks appear to address the mechanisms that explain the need for repeated exercise stimulus to maintain health of functionally diverse cell types such as muscle, vasculature, endothelium and neuronal circuitry. Central to the exercise response is the tissue specific and temporal modulations of metabolic processing of carbohydrates, fats, proteins and oxygen. Those metabolic responses are coupled with simultaneous modulations of genomic and epigenomic expressions that occur in working muscles as well as widely distributed tissues not involved in, or supporting muscle contraction or other exercise functions. We propose that the well-documented therapeutic actions of repeated physical activities over human lifespan are mediated by the rapidly turning-over proto-oncogenic Myc-network of transcription factors. This transcription factor network is unique in utilizing promoter and epigenomic mechanisms for controlling genes that include those encoding intermediary metabolism and mitochondrial functions and coupling their expression with cell growth and proliferation. We further propose that there are two arms of this network that consists of driver cells (e.g., working myocytes) that produce and release lactate and other metabolites of intermediary metabolism which represent autocrine, paracrine or endocrine signals for target recipient cells (e.g., aortic endothelium) in which the network becomes activated. And finally, we propose that lactate released from working muscles and taken up by recipient cells links the two arms of the signaling pathway. Recently discovered contributions of the Myc-network in stem cell development and maintenance further suggests that regular physical activity may prevent age-related diseases. Hence regular physical activities may attenuate the various deleterious effects of the Myc-network on health, the wild-side of the Myc-network, through modulating transcription of genes associated with good health.
Authors:
Kishorchandra Gohil; George A Brooks
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-4-24
Journal Detail:
Title:  American journal of physiology. Endocrinology and metabolism     Volume:  -     ISSN:  1522-1555     ISO Abbreviation:  -     Publication Date:  2012 Apr 
Date Detail:
Created Date:  2012-4-26     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100901226     Medline TA:  Am J Physiol Endocrinol Metab     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
1University of California.
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