RT Journal Article
T1 Pas Kinase Deficiency Triggers Antioxidant Mechanisms in the Liver
A1 Dongil, Pilar
A1 Pérez García, Ana
A1 Hurtado Carneiro, Verónica
A1 Herrero de Dios, Carmen
A1 Blázquez Fernández, Enrique
A1 Álvarez García, Elvira
A1 Sanz Miguel, María Del Carmen
AB Metabolic dysfunction in the liver is the cause of numerous pathologies, which are associated with an altered redox state. PASK (PAS Domain Kinase) is a nutrient and bioenergetic sensor. We contend that PASK could act as an oxidative stress sensor in liver and/or control the metabolic balance, playing a role in the mitochondrial homeostasis. Using PASK-deficient mice, we observed that PASK deficiency promotes antioxidant response mechanisms: a lower production of ROS/RNS under non-fasting conditions, overexpression of genes coding to ROS-detoxifying enzymes and mitochondrial fusion proteins (MnSod Gpx, Mfn1 and Opa1), coactivator Ppargc1a, transcription factors (Pparg and FoxO3a) and deacetylase Sirt1. Also, under fasting conditions, PASK deficiency induced the overexpression of Ppargc1a, Ppara, Pparg, FoxO3a and Nrf2 leading to the overexpression of genes coding to antioxidant enzymes such as MnSOD, Cu/ZnSOD, GPx, HO1 and GCLm. Additionally, inducing PINK1 involved in cell survival and mitophagy. These changes kept ROS steady levels and improved the regenerative state. We suggest a new role for PASK as a controller of oxidative stress and mitochondrial dynamics in the liver. In fact, antioxidant response is PASK dependent. PASK-targeting could therefore be a good way of reducing the oxidative stress in order to prevent or treat liver diseases.
PB Springer
SN 2045-2322
YR 2018
FD 2018-09-14
LK https://hdl.handle.net/20.500.14352/107745
UL https://hdl.handle.net/20.500.14352/107745
LA eng
NO Dongil P, Pérez-García A, Hurtado-Carneiro V, Herrero-de-Dios C, Blazquez E, Alvarez E, Sanz C. Pas Kinase Deficiency Triggers Antioxidant Mechanisms in the Liver. Sci Rep. 2018 Sep 14;8(1):13810. doi: 10.1038/s41598-018-32192-w. PMID: 30217996; PMCID: PMC6138710.
NO Becas de la Universidad Complutense-Programa de Financiación Banco Santander para la Creación y Consolidación de Equipos de Investigación [GR3/14]Fondos FEDER
NO European Commission
NO Universidad Complutense de Madrid
NO Banco Santander
NO Fundación Mutua Madrileña
NO Instituto de Salud Carlos III (España)
DS Docta Complutense
RD 8 abr 2025