Liver HIF-1 Alpha Induction Precedes Apoptosis Following Normothermic Ischemia-Reperfusion in Rats

• Published in: Transplantation proceedings Vol. 40; no. 6; pp. 2042 - 2045
• Main Authors: Cursio, R, Miele, C, Filippa, N, Van Obberghen, E, Gugenheim, J
• Format: Journal Article Conference Proceeding
• Language: English
• Published: New York, NY Elsevier Inc 01.07.2008; Elsevier Science
• Subjects: Animals; Apoptosis - physiology; Biological and medical sciences; Cardiology. Vascular system; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Hypoxia-Inducible Factor 1, alpha Subunit - biosynthesis; Hypoxia-Inducible Factor 1, alpha Subunit - metabolism; In Situ Nick-End Labeling; Liver - cytology; Liver - physiology; Liver - physiopathology; Male; Medical sciences; Rats; Rats, Inbred Lew; Reperfusion Injury - physiopathology; Surgery; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Tissue, organ and graft immunology; Rat; Digestive system; Induction; Liver; Ischemia reperfusion; Rodentia; Transplantation; Medicine; Vertebrata; Mammalia; Treatment; Cell death; Surgery; Animal; Graft; Transcription factor HIF1; Triggering; Apoptosis
• ISSN: 0041-1345; 1873-2623
• DOI: 10.1016/j.transproceed.2008.05.037

Abstract Apoptosis plays an important role in ischemia-reperfusion (I-R) injury during liver transplantation. The hypoxia-inducible factor alpha (HIF-1α) may trigger liver apoptosis following I-R through the induction of hypoxically regulated genes. The aim of this study was to evaluate the effect of normothermic liver I-R on HIF-1α expression and apoptosis in rats. Segmental normothermic ischemia of the liver was induced in rats for 120 minutes. Liver extracts from either ischemic or nonischemic lobes were prepared at 0, 1, 3, and 6 hours after reperfusion. Liver HIF-1α protein expression was examined by Western blot analysis. Liver apoptosis was quantified using terminal deoxynucleotide transferase-mediated deoxyuridine triphosphate nick end labeling assay. Normothermic I-R resulted in a significant ( P < .05) increase in liver HIF-1α protein levels 1 and 3 hours after reperfusion. Liver apoptosis was significantly ( P < .005) increased at 3 and 6 hours after reperfusion. In conclusion, normothermic liver I-R leads to increased liver expression of HIF-1α and apoptosis.