CFTR in cystic fibrosis and cholera: from membrane transport to clinical practice

Goodman, Barbara E.; Percy, W. H.

doi:10.1152/advan.00035.2004

Cited by 30 publications

(26 citation statements)

References 35 publications

(31 reference statements)

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“…The association between high sweat Cl and cystic fibrosis was first recognized by di Sant'Agnese et al in 1953 [165]; and subsequently, a standardized sweat test (Quantitative Pilocarpine Iontophoretic Test) was developed by Gibson and Cooke in 1959 [166]. Individuals with cystic fibrosis have higher than normal sweat [Cl] because of a genetic absence of a functioning CFTR (two defective genes, homozygote) [167][168][169][170]. The cutoff for a positive sweat test consistent with cystic fibrosis is sweat [Cl] >60 mmol/L [171].…”

Section: Sweat Composition As a Biomarkermentioning

confidence: 99%

Physiology of sweat gland function: The roles of sweating and sweat composition in human health

2019

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The purpose of this comprehensive review is to: 1) review the physiology of sweat gland function and mechanisms determining the amount and composition of sweat excreted onto the skin surface; 2) provide an overview of the well-established thermoregulatory functions and adaptive responses of the sweat gland; and 3) discuss the state of evidence for potential non-thermoregulatory roles of sweat in the maintenance and/or perturbation of human health. The role of sweating to eliminate waste products and toxicants seems to be minor compared with other avenues of excretion via the kidneys and gastrointestinal tract; as eccrine glands do not adapt to increase excretion rates either via concentrating sweat or increasing overall sweating rate. Studies suggesting a larger role of sweat glands in clearing waste products or toxicants from the body may be an artifact of methodological issues rather than evidence for selective transport. Furthermore, unlike the renal system, it seems that sweat glands do not conserve water loss or concentrate sweat fluid through vasopressin-mediated water reabsorption. Individuals with high NaCl concentrations in sweat (e.g. cystic fibrosis) have an increased risk of NaCl imbalances during prolonged periods of heavy sweating; however, sweat-induced deficiencies appear to be of minimal risk for trace minerals and vitamins. Additional research is needed to elucidate the potential role of eccrine sweating in skin hydration and microbial defense. Finally, the utility of sweat composition as a biomarker for human physiology is currently limited; as more research is needed to determine potential relations between sweat and blood solute concentrations.

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Section: Sweat Composition As a Biomarkermentioning

confidence: 99%

Physiology of sweat gland function: The roles of sweating and sweat composition in human health

2019

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“…The reduced reabsorption of Na + as well as Cl − is a result of the functional interaction between CFTR and ENaC, as ENaC activation depends on functioning CFTR (Reddy and Quinton 2003). CFTR availability is reduced with defects in CFTR genes (i.e., cystic fibrosis) (Goodman and Percy 2005;Quinton 1999Quinton , 2007Reddy and Quinton 2003;Rowe et al 2005). Thus, with cystic fibrosis, defects in CFTR also impose a loss of ENaC activity (Reddy and Quinton 2003).…”

Section: Reabsorption Mechanismsmentioning

confidence: 99%

Physiological mechanisms determining eccrine sweat composition

2020

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The purpose of this paper is to review the physiological mechanisms determining eccrine sweat composition to assess the utility of sweat as a proxy for blood or as a potential biomarker of human health or nutritional/physiological status. Methods This narrative review includes the major sweat electrolytes (sodium, chloride, and potassium), other micronutrients (e.g., calcium, magnesium, iron, copper, zinc, vitamins), metabolites (e.g., glucose, lactate, ammonia, urea, bicarbonate, amino acids, ethanol), and other compounds (e.g., cytokines and cortisol). Results Ion membrane transport mechanisms for sodium and chloride are well established, but the mechanisms of secretion and/or reabsorption for most other sweat solutes are still equivocal. Correlations between sweat and blood have not been established for most constituents, with perhaps the exception of ethanol. With respect to sweat diagnostics, it is well accepted that elevated sweat sodium and chloride is a useful screening tool for cystic fibrosis. However, sweat electrolyte concentrations are not predictive of hydration status or sweating rate. Sweat metabolite concentrations are not a reliable biomarker for exercise intensity or other physiological stressors. To date, glucose, cytokine, and cortisol research is too limited to suggest that sweat is a useful surrogate for blood. Conclusion Final sweat composition is not only influenced by extracellular solute concentrations, but also mechanisms of secretion and/or reabsorption, sweat flow rate, byproducts of sweat gland metabolism, skin surface contamination, and sebum secretions, among other factors related to methodology. Future research that accounts for these confounding factors is needed to address the existing gaps in the literature.

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“…Heterozygous individuals (carriers), with one WT gene and one F508del mutated gene, have no symptoms and there may have been some selective advantage in the past for such individuals—such as reduced water loss in diarrhea. This has led to a theory that the prevalence of this mutation in certain populations is due to the increased resistance to dehydration-causing diseases such as cholera and typhoid fever which were previously major causes of morbidity, especially in infancy [9]. …”

Section: The Effects On Stability Of F508 Deletionmentioning

confidence: 99%

The cystic fibrosis transmembrane conductance regulator (CFTR) and its stability

Meng

Clews

Kargas

et al. 2016

Cell. Mol. Life Sci.

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The cystic fibrosis transmembrane conductance regulator (CFTR) is responsible for the disease cystic fibrosis (CF). It is a membrane protein belonging to the ABC transporter family functioning as a chloride/anion channel in epithelial cells around the body. There are over 1500 mutations that have been characterised as CF-causing; the most common of these, accounting for ~70 % of CF cases, is the deletion of a phenylalanine at position 508. This leads to instability of the nascent protein and the modified structure is recognised and then degraded by the ER quality control mechanism. However, even pharmacologically ‘rescued’ F508del CFTR displays instability at the cell’s surface, losing its channel function rapidly and it is rapidly removed from the plasma membrane for lysosomal degradation. This review will, therefore, explore the link between stability and structure/function relationships of membrane proteins and CFTR in particular and how approaches to study CFTR structure depend on its stability. We will also review the application of a fluorescence labelling method for the assessment of the thermostability and the tertiary structure of CFTR.

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CFTR in cystic fibrosis and cholera: from membrane transport to clinical practice

Cited by 30 publications

References 35 publications

Physiology of sweat gland function: The roles of sweating and sweat composition in human health

Physiology of sweat gland function: The roles of sweating and sweat composition in human health

Physiological mechanisms determining eccrine sweat composition

The cystic fibrosis transmembrane conductance regulator (CFTR) and its stability

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