Indirubin and NAD
| Autor: | João Soeiro, Teodoro, Ana Teresa, Varela, Filipe Valente, Duarte, Ana Patrícia, Gomes, Carlos Marques, Palmeira, Anabela Pinto, Rolo |
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| Rok vydání: | 2017 |
| Předmět: |
Antibiotics
Antineoplastic Glycogen Synthase Kinase 3 beta Indoles Cytochromes c Mitochondria Liver NAD Rats Rats Zucker Fatty Liver Cyclophilins Adenosine Triphosphate Hepatic Artery Liver Reperfusion Injury Oximes Animals Sirtuins Calcium Warm Ischemia Reactive Oxygen Species Mitochondrial ADP ATP Translocases Cyclophilin D |
| Zdroj: | European journal of clinical investigation. 48(6) |
| ISSN: | 1365-2362 |
| Popis: | Fatty livers are considerably more susceptible to acute stressors, such as ischaemia/reperfusion (I/R). As the incidence of I/R is high due to surgical events and some pathologies, there is an urgent need to find strategies against I/R injury (I/RI) in fatty livers. We postulate that an acute pretreatment with indirubin-3'-oxime (Ind) or NADZucker fatty rats were subjected to warm ischaemia and 12 hours of reperfusion. Ind or NADPretreatment decreased markers of liver injury while preserving mitochondrial cytochrome c content, which is related to the prevention of calcium-induced mitochondrial permeability transition (mPT), the decline in mitochondrial respiratory state 3 and ATP content. The generation of reactive oxygen species (ROS) was also diminished. Inhibition of GSK-3ß by Ind resulted in the prevention of cyclophilin-D (CypD) phosphorylation, unabling it to bind to the adenine nucleotide translocator (ANT), thus, preventing mPT induction. Furthermore, deacetylation of CypD at Lys residue by sirtuin 3 (SIRT3) caused its dissociation from ANT, contributing to an increase in mPT threshold in NADPretreatment with Ind or NAD |
| Databáze: | OpenAIRE |
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