The intestinal epithelium is able to adapt to varying blood flow and, thus, oxygen availability.
Still, the adaptation fails under pathologic situations. A better understanding of the mechanisms
underlying the epithelial adaptation to hypoxia could help to improve the therapeutic approach.
We hypothesized that the short-term adaptation to hypoxia is mediated via AMP-activated protein
kinase (AMPK) and that it is coupled to the long-term adaptation by a common regulation mechanism,
the HIF-hydroxylase enzymes. Further, we hypothesized the transepithelial transport of glucose
to be part of this short-term adaptation. We conducted Ussing chamber studies using isolated
lagomorph jejunum epithelium and cell culture experiments with CaCo-2 cells. The epithelia and
cells were incubated under 100% and 21% O2, respectively, with the panhydroxylase inhibitor
dimethyloxalylglycine (DMOG) or under 1% O2. We showed an activation of AMPK under hypoxia
and after incubation with DMOG by Western blot. This could be related to functional effects like an
impairment of Na+-coupled glucose transport. Inhibitor studies revealed a recruitment of glucose
transporter 1 under hypoxia, but not after incubation with DMOG. Summing up, we showed an
influence of hydroxylase enzymes on AMPK activity and similarities between hypoxia and the effects
of hydroxylase inhibition on functional changes.
| Identifer | oai:union.ndltd.org:DRESDEN/oai:qucosa:de:qucosa:88934 |
| Date | 10 January 2024 |
| Creators | Dengler, Franziska, Gäbel, Gotthold |
| Publisher | MDPI |
| Source Sets | Hochschulschriftenserver (HSSS) der SLUB Dresden |
| Language | English |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, doc-type:article, info:eu-repo/semantics/article, doc-type:Text |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | 4993, 10.3390/ijms20204993 |
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