Not Only Mutated CFTR Gene, But Also Cell Hypoxia Is Necessary for Cystic Fibrosis to Develop

Published: 08th June 2011
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Low body oxygen affects all cells and organs in the human body. It is commonly known and proven in medicine that diminished tissue oxygenation results in diabetes, obesity, insulin resistance, suppressed immune system, chronic inflammation, angina pectoris pain, chronic fatigue, allergies, cancer and many other effects.





It has been recognized so far that cystic fibrosis is the result of a malfunctioning genetic factor (CFTR - cystic fibrosis transmembrane conductance regulator). This genetic factor causes the organs to generate abnormally heavy and glue-like mucus due to ineffective work of the pumps that transport water, together with ions of sodium and chloride, across the epithelial surfaces. This thick mucus builds up in the airways of the lungs and in the pancreas, the organ that helps to break down food. This results in threatening lung bacterial infections and serious gastrointestinal troubles.





A novel scientific breakthrough, based on several medical studies, states that expression of the cystic fibrosis CFTR mutation gene is governed, in a dose-dependent manner, by diminished cells oxygen content.





A team of North American doctors from the Department of Genetics in the University of Alabama (Birmingham) investigated the Role of oxygen availability in CFTR expression and function (Guimbellot et al, 2008). In the abstract, these doctors wrote, "... In the present study, we investigated regulation of CFTR mRNA during oxygen restriction, examined effects of hypoxic signaling on chloride transport across cell monolayers, and related these findings to a possible role in the pathogenesis of chronic hypoxic lung disease. CFTR mRNA, protein, and function were robustly and reversibly altered in human cells in relation to hypoxia... Environmental factors that induce hypoxic signaling regulate CFTR mRNA and epithelial Cl(-) transport in vitro and in vivo."





This study claimed that low oxygen level is the main factor that control CFTR work and composition of the mucus.





In 2009, German biomedical scientists from the Department of Gastroenterology, Hepatology, and Endocrinology (Hanover Medical High School) also confirmed the effect of Hypoxia inducible factor-1 (HIF-1)-mediated repression of cystic fibrosis transmembrane conductance regulator (CFTR) in the intestinal epithelium (Zheng et al, 2009). They wrote, " ... Consequently, HIF-1 overexpressing cells exhibited significantly reduced transport capacity in colorimetric Cl(-) efflux studies, altered short circuit measurements, and changes in transepithelial fluid movement. Whole-body hypoxia in wild-type mice resulted in significantly reduced small intestinal fluid and HCO(3)(-) secretory responses to forskolin... In summary, our study clarifies CFTR regulation and introduces the concept of a HIF-1-orchestrated response designed to regulate ion and fluid movement across hypoxic intestinal epithelia".





American research scientists from the Department of Medicine in the University of Alabama (Birmingham) tested the outcomes of cell oxygen concentrations on CFTR in vitro. The heading of their article in the American Journal of Physiology and Cell Physiology, states that Improved oxygenation promotes CFTR maturation and trafficking in MDCK monolayers (Bebök et al, 2001). Inside their abstract, the scientists wrote, "Together, our data indicate that improved cellular oxygenation can increase endogenous CFTR maturation and/or trafficking".





It is, therefore, a proven medical fact now that cystic fibrosis develops due to low level of oxygen in body cells. As a next step, we can focus on causes of cell hypoxia. Why do people with cystic fibrosis develop tissue hypoxia? Several medical studies measured minute ventilation rates in groups of people with cystic fibrosis. It was found in all these studies that they had from 10 up to 18 L/min for their ventilation rates. But the medical norm is only 6-7 Liters of air per minute for quiet breathing at rest. Therefore, people with cystic fibrosis experience or suffer from chronic hyperventilation (breathing more than the medical standards). What are the effects?





To begin with, bear in mind that normal breathing delivers virtually maximum oxygenation of the arterial blood (approximately 98%). If people breathe more, they usually diminish oxygen concentration in the arterial blood. How could it be? It is simple to discover, that deep and big breathing is done employing the upper chest muscles. As a result, the lower areas of the lungs do not obtain fresh air supply with higher oxygen content. Consequently, oxygenation of the arterial blood is reduced even though breathing is larger and heavier.





Secondly, we actually lower the amount of carbon dioxide or CO2 in the arterial blood. This gas is a dilator of blood vessels (search the web for "CO2-vasodilation" effect). CO2 is also fundamental for release of oxygen in tissues due to the Bohr effect. As a result, less blood arrives to tissues of all vital organs and, in addition, less oxygen is released due to the suppressed Bohr effect. These are the direct effects of arterial hypocapnia (low CO2 in arterial blood). However, low CO2 in the lungs cause effects in the bronchi and alveoli: bronchospasm and chronic inflammation, as well as inability of the immune system to heal lung tissues.





This medical analysis proves that hyperventilation is the cause of cell hypoxia. There are many methods and techniques to slow down breathing back to the medical norm and increase oxygen levels in cells. These include the Amazing DIY breathing device, Oxygen Remedy, the Frolov breathing device and Buteyko breathing exercises.





Resources from NormalBreathing.com


Cystic Fibrosis and Hypoxia : Causes, Effects, and Treatment – Main 34-pages article about cystic fibrosis.


Cystic Fibrosis Therapy - with links to several web pages about cystic fibrosis.


COPD breathing exercises with clinical trials results.





NormalBreathing.com has many hundreds of medical quotes and references, graphs and charts, tables and analysis of numerous respiratory techniques, results of clinical trials and free breathing exercises, lifestyle modules, manuals, techniques, and other resources to increase brain and body oxygen levels and improve health.




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