Full Professor (1978), University of Chile
Sc. (1972) University of Toronto, Ontario, Canada
Biochemist (1970) University of Chile.
Research project: T3 liver preconditioning (PC) is a strategy to prevent liver injury induced by ischemia-reperfusion (IR) associated with tissue resection, transplantation or trauma. Thyroid hormone (T3)-PC involves up-regulation of signaling cascades related to NF-kB, STAT3, AP-1, and Nrf2 redox-activation, leading to enhanced expression of cytoprotective proteins and cell proliferation. Currently, our research is based on the high energy demands required for liver PC underlying induction of antioxidant, anti-apoptotic, anti-inflammatory, and acute-phase protein components, hepatocyte and Kupffer-cell proliferation, and repair or re-synthesis of damaged biomolecules.
In this research project, we aimed to evaluate the effects of T3 on liver AMP-activated protein kinase [AMPK] signaling cascade as a crucial mechanism limiting excessive ATP utilization and promoting ATP production. AMPK activation [AMPK(+)] in these conditions will support liver PC against IR injury through coordination of hepatic energy metabolism by convergence of regulatory signals monitoring cellular energy status.
For these purposes, Specific Goals include the evaluation of: (1) the kinetic pattern of liver AMPK(+) in relation to up-regulation of the upstream AMPK activators CaMKKb, TAK1, and LKB1, LKB1 stabilizers (STRAD and MO25), and the AMP/ATP ratio; (2) role of T3-induced oxidative stress on liver AMPK(+) cascade, assessed by pretreatment with the antioxidant N-acetylcysteine prior to T3; (3) the phosphorylation status of key AMPK targets related to lipid metabolism at times of maximal AMPK(+), namely, acetylCoA carboxylase, CREB, and PPAR-g-coactivator-1a (PGC-1a), and the mRNA levels of AMPK and PGC-1a; (4) the protein and/or mRNA expression of liver enzymes related to fatty acid oxidation (carnitine-palmitoyltransferase-1a, mitochondrial thioesterase-1, and acyl-CoA oxidase (ACO)) and rates of hepatic mitochondrial fatty acid oxidation; and (5) the role of AMPK(+) on T3-induced liver preconditioning in the model of partial hepatic IR injury, either without or with in vivo pretreatment with the AMPK inhibitor Compound-C.
CORNEJO P, VARGAS R, VIDELA LA, 2013 “Nrf2-regulated phase-II detoxification enzymes and phase-III transporters are induced by thyroid hormone in rat liver”. Biofactors 39: 514-521 (2013). ISSN: 1872-8081 IF: 4.592
PILONI NE, FERNANDEZ V, VIDELA LA, PUNTARULO S,. 2013. “Acute iron overload and oxidative stress in brain”. Toxicology 314: 174-182 (2013). ISSN: 0300-483X. IF: 3.621
VARGAS R, ORTEGA Y, BOZO V, ANDRADE M, MINUZZI G, CORNEJO P, FERNÁNDEZ V, VIDELA LA, 2013. “Thyroid hormone activates rat liver adenosine 5,-monophosphate-activated protein kinase (AMPK): relation to CaMKKβ, TAK1, and LKB1 expression and energy status”. Journal of Biological Regulators and Homeostatic Agents 27 (2013) 989-999. ISSN: 0393-974X. IF: 2.406
MORALES P, VARGAS R, VIDELA LA, FERNÁNDEZ V, 2014. “Nrf2 activation in the liver of rats subjected to a preconditioning sub-chronic iron protocol”. Food & Function 5 (2014) 243-250. ISSN: 2042-6496. IF: 2.791
TAPIA G, VALENZUELA R, ESPINOSA A, ROMANQUE P, DOSSI C, GONZALEZ-MAÑÁN D, VIDELA LA, D,ESPESSAILLES A, 2014. “N-3 long-chain PUFA supplementation prevents high fat diet induced mouse liver steatosis and inflammation in relation to PPAR-α upregulation and NF-κB DNA binding abrogation”. Molecular Nutrition & Food Research 58 (2014) 1333-1341. ISSN: 1613-4133. IF:4.603
DOSSI CG, TAPIA G, ESPINOSA A, VIDELA LA, D,ESPESSAILLES A, 2014. “Reversal of high-fat diet-induced hepatic steatosis by n-3 LCPUFA: role of PPAR-α and SREBP-1c”. Journal of Nutritional Biochemistry 25 (2014) 977-984. ISSN: 0955-2863 IF: 3.794
VIDELA LA, FERNÁNDEZ V, CORNEJO P, VARGAS R, MORALES P, CEBALLO J, FISCHER A, ESCUDERO N, ESCOBAR O, “T3-induced liver AMP-activated protein kinase signaling: redox dependency and upregulation of downstream targets”. World Journal of Gastroenterology 20 (2014) 17416-17425. ISSN: 1007-9327. IF: 2.369
PEDEMONTE JC, VARGAS R, CASTILLO V, HODALI S, GUTIERREZ G, TAPIA G, CASTILLO I, VIDELA LA, FERNÁNDEZ V, A 2015. “combined iron and thyroid hormone protocol suppresses ischemia-reperfusion injury in rat livers”. RSC Advances 5 (2015) 26209-26217. ISSN: 2046-2069. IF: 3.84
VALENZUELA R, BARRERA C, ESPINOSA A, LLANOS P, ORELLANA P, VIDELA LA, 2015. “Reduction in the desaturation capacity of the liver in mice subjected to high fat diet: relation to LCPUFA depletion in liver and extrahepatic tissues”. Prostaglandins, Leukotrienes and Essential Fatty Acids 98 (2015) 7-14. ISSN: 0952-3278. IF: 2.346
VIDELA LA, FERNÁNDEZ V, CORNEJO P, VARGAS R, CASTILLO I, 2015. “Thyroid hormone in the frontier of cell protection, survival and functional recovery”. Expert Reviews in Molecular Medicine vol. 17 (2015), e10, 1-12. ISSN: 1462-399. IF: 5.152