Electrogenic transport, oxygen consumption, and sensitivity to acute hypoxia of human colonic epithelium

Carra, Graciela E; Ibáñez, Jorge E; Saraví, Fernando D.

doi:10.1007/s00384-011-1215-7

Cited by 15 publications

(15 citation statements)

References 30 publications

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“…With regard to general intestinal function, both intestinal absorption and permeability were shown to be modified by environmental oxygen concentration [41,42] . Moreover, hypoxic conditions were shown to directly affect electrical currents when applied to the intestinal tissue from the serosa side [43] , suggesting a direct effect of oxygen concentration on ion transport in the gut epithelium. Intriguingly, the induction of 'hypoxia-type' signaling by the inflammatory microenvironment in colitis has been observed, a phenomenon commonly referred to as 'inflammatory hypoxia' [20,44] .…”

Section: Key Messagesmentioning

confidence: 99%

High Altitude Journeys, Flights and Hypoxia: Any Role for Disease Flares in IBD Patients?

Vavricka

Rogler

Biedermann

2016

Dig Dis

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The importance of environmental factors in the pathogenesis including their disease-modifying potential are increasingly recognized in inflammatory bowel disease (IBD) patients, largely driven by the perception that the prevalence and incidence of IBD are on the rise within the last few years, especially in non-western countries. One of those factors is believed to be hypoxia. The role of hypoxia as a modifying or even causative factor in the genesis and maintenance of inflammation has been increasingly elucidated in recent years. Hypoxia is believed to be a main inducing factor of inflammation. This has been studied in different animal experiments as well as in humans exposed to hypoxia. In several studies -mainly in mice -animals exposed to short-term hypoxia accumulated inflammatory cells in multiple organs and showed elevated cytokines in the blood. Comparable studies were performed in humans, mainly in healthy mountaineers. Recently, we reported on the association between IBD flare-up episodes and antecedent journeys to high-altitude region and aircraft travels. According to these findings, we concluded that flights and stays at high altitudes of >2,000 mg are a risk factor for increased disease activity in IBD. To evaluate the potential influence of hypoxia on the course of IBD on a biomolecular level and to test the effects of hypoxia under standardized conditions, we initiated a prospective and controlled investigation in both healthy controls and IBD patients in stable remission. The study participants underwent a 3-hour exposure to hypoxic conditions simulating an altitude of 4,000 m above sea level in a hyperbaric pressure chamber and clinical parameters as well as blood and stool samples were collected at several time points. The first results of this study are expected in the near future. studies -mainly in mice -animals exposed to short-term hypoxia accumulated inflammatory cells in multiple organs and showed elevated cytokines in the blood. Comparable studies were performed in humans, mainly in healthy mountaineers. Recently, we reported on the association between IBD flare-up episodes and antecedent journeys to high-altitude region and aircraft travels. According to these findings, we concluded that flights and stays at high altitudes of >2,000 mg are a risk factor for increased disease activity in IBD. To evaluate the potential influence of hypoxia on the course of IBD on a biomolecular level and to test the effects of hypoxia under standardized conditions, we initiated a prospective and controlled investigation in both healthy controls and IBD patients in stable remission. The study participants underwent a 3-hour exposure to hypoxic conditions simulating an altitude of 4,000 m above sea level in a hyperbaric pressure chamber and clinical parameters as well as blood and stool samples were collected at several time points. The first results of this study are expected in the near future. AbstractThe importance of environmental factors in the pathogenesis including their disease-modifyi...

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Section: Key Messagesmentioning

confidence: 99%

High Altitude Journeys, Flights and Hypoxia: Any Role for Disease Flares in IBD Patients?

Vavricka

Rogler

Biedermann

2016

Dig Dis

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“…This suggests that the asymmetry is also not due to the specific ion being transported but represents a physiological characteristic of the colonic epithelium. It should be noted that this asymmetry has also been demonstrated in epithelial samples from human sigmoid colon[18]. …”

Section: Discussionmentioning

confidence: 77%

Rectification of oxygen transfer through the rat colonic epithelium

Saraví

Carra

Matus

et al. 2017

WJGP

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AIMTo assess whether higher sensitivity of colonic epithelium to hypoxia at the serosal side is associated with oxygen transfer asymmetry.METHODSRats were fed either with normal chow or a low-sodium diet. Tissues were mounted as flat sheets in a modified, airtight Ussing chamber with oxygen meters in each hemichamber. Mucosal samples from normal diet animals were studied under control conditions, in low-chloride solution and after adding chloride secretion inhibitors and chloride secretagogues. Samples from sodium-deprived rats were studied before and after ouabain addition. In separate experiments, the correlation between short-circuit current and oxygen consumption was analyzed. Finally, hypoxia was induced in one hemichamber to assess the relationship between its oxygen content and the oxygen pressure difference between both hemichambers.RESULTSIn all studied conditions, oxygen consumption was larger in the serosal hemichamber than in the mucosal one (P = 0.0025 to P < 0.0001). Short-circuit current showed significant correlation with both total oxygen consumption (r = 0.765; P = 0.009) in normoxia and oxygen consumption in the serosal hemichamber (r = 0.754; P = 0.011) during mucosal hypoxia, but not with oxygen consumption in the mucosal hemichamber. When hypoxia was induced in the mucosal hemichamber, an oxygen pressure difference of 13 kPa with the serosal hemichamber was enough to keep its oxygen content constant. However, when hypoxia was induced in the serosal hemichamber, the oxygen pressure difference with the mucosal hemichamber necessary to keep its oxygen content constant was 40 kPa (P < 0.0001).CONCLUSIONSerosal oxygen supply is more readily available to support short-circuit current. This may be partly due to a rectifying behavior of transepithelial oxygen transfer.

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“…Many of the transporting functions of the intestinal epithelium are highly energy-demanding, none more so than that of the Na + /K + -ATPase pump. The oxygen demand of the Na + /K + -ATPase is such that in the sigmoid colon, it is reported to consume 26% of available oxygen under basal conditions (Carra et al 2011), whereas it can demand 20% of available ATP in resting duodenum (Milligan & McBride, 1985). Despite the fact that the pump is the primary driving force for intestinal epithelial transport processes, there is still little known of its regulation in conditions associated with intestinal hypoxia.…”

Section: Regulation Of Epithelial Transport Processes In Hypoxiamentioning

confidence: 99%

Oxygen in the regulation of intestinal epithelial transport

Ward

Keely

2014

The Journal of Physiology

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The transport of fluid, nutrients and electrolytes to and from the intestinal lumen is a primary function of epithelial cells. Normally, the intestine absorbs approximately 9 l of fluid and 1 kg of nutrients daily, driven by epithelial transport processes that consume large amounts of cellular energy and O 2 . The epithelium exists at the interface of the richly vascularised mucosa, and the anoxic luminal environment and this steep O 2 gradient play a key role in determining the expression pattern of proteins involved in fluid, nutrient and electrolyte transport. However, the dynamic nature of the splanchnic circulation necessitates that the epithelium can evoke co-ordinated responses to fluctuations in O 2 availability, which occur either as a part of the normal digestive process or as a consequence of several pathophysiological conditions. While it is known that hypoxia-responsive signals, such as reactive oxygen species, AMP-activated kinase, hypoxia-inducible factors, and prolyl hydroxylases are all important in regulating epithelial responses to altered O 2 supply, our understanding of the molecular mechanisms involved is still limited. Here, we aim to review the current literature regarding the role that O 2 plays in regulating intestinal transport processes and to highlight areas of research that still need to be addressed.

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Electrogenic transport, oxygen consumption, and sensitivity to acute hypoxia of human colonic epithelium

Abstract: The present results allow a better understanding of the clinical consequences of acute hypoxia on intestinal ion transport.

Cited by 15 publications

References 30 publications

High Altitude Journeys, Flights and Hypoxia: Any Role for Disease Flares in IBD Patients?

High Altitude Journeys, Flights and Hypoxia: Any Role for Disease Flares in IBD Patients?

Rectification of oxygen transfer through the rat colonic epithelium

Oxygen in the regulation of intestinal epithelial transport

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