Adaptive mechanisms in no flow vs. low flow ischemia in equine jejunum epithelium: Different paths to the same destination.
Abstract: Intestinal ischemia reperfusion injury (IRI) is a frequent complication of equine colic. Several mechanisms may be involved in adaptation of the intestinal epithelium to IRI and might infer therapeutic potential, including hypoxia-inducible factor (HIF) 1α, AMP-activated protein kinase (AMPK), nuclear factor-erythroid 2-related factor 2 (NRF2), and induction of autophagy. However, the mechanisms supporting adaptation and thus cellular survival are not completely understood yet. We investigated the activation of specific adaptation mechanisms in both no and low flow ischemia and reperfusion simulated in equine jejunum epithelium in vivo. We found an activation of HIF1α in no and low flow ischemia as indicated by increased levels of HIF1α target genes and phosphorylation of AMPKα tended to increase during ischemia. Furthermore, the protein expression of the autophagy marker LC3B in combination with decreased expression of nuclear-encoded mitochondrial genes indicates an increased rate of mitophagy in equine intestinal IRI, possibly preventing damage by mitochondria-derived reactive oxygen species (ROS). Interestingly, ROS levels were increased only shortly after the onset of low flow ischemia, which may be explained by an increased antioxidative defense, although NFR2 was not activated in this setup. In conclusion, we could demonstrate that a variety of adaptation mechanisms manipulating different aspects of cellular homeostasis are activated in IRI irrespective of the ischemia model, and that mitophagy might be an important factor for epithelial survival following small intestinal ischemia in horses that should be investigated further.
Copyright © 2022 Dengler, Sternberg, Grages, Kästner and Verhaar.
Publication Date: 2022-09-08 PubMed ID: 36157182PubMed Central: PMC9493374DOI: 10.3389/fvets.2022.947482Google Scholar: Lookup
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Summary
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The research article discusses the different adaptive mechanisms observed in both no flow and low flow ischemia conditions in the equine jejunum epithelium connected to intestinal ischemia reperfusion injury (IRI), which is a common problem with equine colic. They discovered that several adaptation mechanisms are apprehended during IRI irrespective of the ischemia model, indicating that mitophagy could be key for epithelial survival.
Adaptive Mechanisms in Intestinal Ischemia Reperfusion Injury
- The researchers investigate the adaptive methods of the intestinal epithelium to Intestinal Ischemia Reperfusion Injury (IRI), a common issue linked to equine colic. This injury results from reduced blood flow, causing tissue damage and subsequent inflammation when the blood reinstates.
- They look into specific mechanisms, including hypoxia-inducible factor 1α (HIF1α), AMP-activated protein kinase (AMPK), nuclear factor-erythroid 2-related factor 2 (NFR2), and autophagy induction. These mechanisms support adaptation and cellular survival, though their operations are not fully comprehended.
- The activation of these mechanisms is examined in different conditions of no and low flow ischemia (a lack of blood flow and reduced blood flow, respectively), and their reperfusion (restoration of blood flow), specifically in the equine jejunum epithelium (part of the small intestine in horses).
Findings and Implications
- The findings illustrate an activation of HIF1α in both no flow and low flow ischemia. This conclusion is drawn from observed elevated levels of HIF1α target genes and a tendency of AMPKα phosphorylation to increase during ischemia.
- The researchers also find an increased rate of mitophagy (a type of autophagy where cells recycle their own components) in equine intestinal IRI, indicated by the protein expression of the autophagy marker LC3B alongside a reduced expression of nuclear-encoded mitochondrial genes.
- This could suggest that mitophagy could help prevent damage caused by reactive oxygen species (ROS) originating from the mitochondria.
- ROS levels were observed to increase briefly at the onset of low flow ischemia. This could be due to an increased antioxidative defense, although NFR2 was not activated in this situation.
- The variety of adaptive mechanisms demonstrated in this research elucidates different aspects of cellular homeostasis and highlights the potential importance of mitophagy in terms of epithelial survival after small intestinal ischemia in horses, an area which requires further investigation.
Cite This Article
APA
Dengler F, Sternberg F, Grages M, Kästner SB, Verhaar N.
(2022).
Adaptive mechanisms in no flow vs. low flow ischemia in equine jejunum epithelium: Different paths to the same destination.
Front Vet Sci, 9, 947482.
https://doi.org/10.3389/fvets.2022.947482 Publication
Researcher Affiliations
- Department of Biochemical Sciences, Institute of Physiology, Pathophysiology and Biophysics, University of Veterinary Medicine, Vienna, Austria.
- Department of Biochemical Sciences, Institute of Physiology, Pathophysiology and Biophysics, University of Veterinary Medicine, Vienna, Austria.
- Clinic for Horses, University of Veterinary Medicine Hannover, Hannover, Germany.
- Clinic for Horses, University of Veterinary Medicine Hannover, Hannover, Germany.
- Small Animal Clinic, University of Veterinary Medicine Hannover, Hannover, Germany.
- Clinic for Horses, University of Veterinary Medicine Hannover, Hannover, Germany.
Conflict of Interest Statement
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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Citations
This article has been cited 3 times.- Windhaber C, Heckl A, Csukovich G, Pratscher B, Burgener IA, Biermann N, Dengler F. A matter of differentiation: equine enteroids as a model for the in vivo intestinal epithelium. Vet Res 2024 Mar 16;55(1):30.
- Dengler F, Domenig O, Kather S, Burgener IA, Steiner JM, Heilmann RM. Dysregulation of intestinal epithelial electrolyte transport in canine chronic inflammatory enteropathy and the role of the renin-angiotensin-aldosterone-system. Front Vet Sci 2023;10:1217839.
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