title: Subnormothermic Perfusion in the Isolated Rat Liver Preserves the Antioxidant Glutathione and Enhances the Function of the Ubiquitin Proteasome System.
abstract: The reduction of oxidative stress is suggested to be one of the main mechanisms to explain the benefits of subnormothermic perfusion against ischemic liver damage. In this study we investigated the early cellular mechanisms induced in isolated rat livers after 15 min perfusion at temperatures ranging from normothermia (37°C) to subnormothermia (26°C and 22°C). Subnormothermic perfusion was found to maintain hepatic viability. Perfusion at 22°C raised reduced glutathione levels and the activity of glutathione reductase; however, lipid and protein oxidation still occurred as determined by malondialdehyde, 4-hydroxynonenal-protein adducts, and advanced oxidation protein products. In livers perfused at 22°C the lysosomal and ubiquitin proteasome system (UPS) were both activated. The 26S chymotrypsin-like (β5) proteasome activity was significantly increased in the 26°C (46%) and 22°C (42%) groups. The increased proteasome activity may be due to increased Rpt6 Ser120 phosphorylation, which is known to enhance 26S proteasome activity. Together, our results indicate that the early events produced by subnormothermic perfusion in the liver can induce oxidative stress concomitantly with antioxidant glutathione preservation and enhanced function of the lysosomal and UPS systems. Thus, a brief hypothermia could trigger antioxidant mechanisms and may be functioning as a preconditioning stimulus.
authors: Department of Cell Biology, Physiology and Immunology, University of Barcelona, Avda Diagonal 643, 08028 Barcelona, Spain.
authors: Teresa
authors: 0000-0002-7131-3667
authors: T
authors: Carbonell
authors: Department of Cell Biology, Physiology and Immunology, University of Barcelona, Avda Diagonal 643, 08028 Barcelona, Spain.
authors: Norma
authors: N
authors: Alva
authors: Department of Cell Biology, Physiology and Immunology, University of Barcelona, Avda Diagonal 643, 08028 Barcelona, Spain.
authors: Sergio
authors: S
authors: Sanchez-Nuño
authors: Department of Physiology, Neurobiology and Behavior, University of California, Davis, 176 Briggs Hall, One Shields Avenue, Davis, CA 95616, USA.
authors: Shannamar
authors: S
authors: Dewey
authors: Department of Physiology, Neurobiology and Behavior, University of California, Davis, 176 Briggs Hall, One Shields Avenue, Davis, CA 95616, USA.
authors: Aldrin V
authors: AV
authors: Gomes
mesh_terms: D000074183:ATPases Associated with Diverse Cellular Activities; D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D002401:Cathepsin B / Q000378:metabolism; D056668:Cathepsin L / Q000378:metabolism; D003080:Cold Temperature; D005978:Glutathione / Q000378:metabolism*; D066298:In Vitro Techniques; D008099:Liver / Q000378:metabolism*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D018384:Oxidative Stress; D010766:Phosphorylation; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D025801:Ubiquitin / Q000378:metabolism*
chemical_list: D000975:Antioxidants; C491454:Psmc5 protein, rat; D025801:Ubiquitin; D008315:Malondialdehyde; D002401:Cathepsin B; D056668:Cathepsin L; D046988:Proteasome Endopeptidase Complex; D000074183:ATPases Associated with Diverse Cellular Activities; D005978:Glutathione