Characterizing Autophagy in the Cold Ischemic Injury of Small Bowel Grafts: Evidence from Rat Jejunum
Autor: | Péter Hardi, György Sétáló, Luca Erlitz, Ildikó Takács, Vivien Telek, Gábor Jancsó, Mónika Vecsernyés, Ibitamuno Caleb, Tibor Nagy |
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Jazyk: | angličtina |
Rok vydání: | 2021 |
Předmět: |
0301 basic medicine
autophagy Endocrinology Diabetes and Metabolism Ischemia Cold storage mucosal injury small bowel grafts 030230 surgery Pharmacology ischemia–reperfusion Microbiology Biochemistry Article 03 medical and health sciences 0302 clinical medicine Medicine Cold preservation Molecular Biology Rat Jejunum business.industry Autophagy apoptosis Ischemic injury Hypoxia (medical) medicine.disease QR1-502 cold preservation 030104 developmental biology Apoptosis medicine.symptom business |
Zdroj: | Metabolites Metabolites, Vol 11, Iss 396, p 396 (2021) Volume 11 Issue 6 |
ISSN: | 2218-1989 |
Popis: | Cold ischemic injury to the intestine during preservation remains an unresolved issue in transplantation medicine. Autophagy, a cytoplasmic protein degradation pathway, is essential for metabolic adaptation to starvation, hypoxia, and ischemia. It has been implicated in the cold ischemia (CI) of other transplantable organs. This study determines the changes in intestinal autophagy evoked by cold storage and explores the effects of autophagy on ischemic grafts. Cold preservation was simulated by placing the small intestines of Wistar rats in an IGL-1 (Institute George Lopez) solution at 4 °C for varying periods (3, 6, 9, and 12 h). The extent of graft preservation injury (mucosal and cellular injury) and changes in autophagy were measured after each CI time. Subsequently, we determined the differences in apoptosis and preservation injury after activating autophagy with rapamycin or inhibiting it with 3-methyladenine. The results revealed that ischemic injury and autophagy were induced by cold storage. Autophagy peaked at 3 h and subsequently declined. After 12 h of storage, autophagic expression was reduced significantly. Additionally, enhanced intestinal autophagy by rapamycin was associated with less tissue, cellular, and apoptotic damage during and after the 12-h long preservation. After reperfusion, grafts with enhanced autophagy still presented with less injury. Inhibiting autophagy exhibited the opposite trend. These findings demonstrate intestinal autophagy changes in cold preservation. Furthermore, enhanced autophagy was protective against cold ischemia–reperfusion damage of the small bowels. |
Databáze: | OpenAIRE |
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