Research Groups

Oxidative and Nitrosative Stress in Acute and Chronic Liver Disease

Scientific Production and Human Team

Principal Investigator

Dr. Manuel de la Mata García

CIBER on Liver and Digestive Diseases (CIBERehd)

PAIDI CTS-273 scientific group

Co-Principal Investigator

Dr. Jose Antonio Bárcena Ruiz

PAIDI BIO-216 scientific group

Oxidative and Nitrosative Stress in Acute and Chronic Liver Disease

Scientific Activity

The members of the research team are divided into the BIO-216 and the CTS-273 scientific group –within the Andalusian Research Plan– and the CIBER for liver and digestive diseases (CIBERehd) in the context of a mixed group consisting of a healthcare team made up of hepatologists, surgeons and a biomedical research team of the HURS Research Unit and Department of Biochemistry and Molecular Biology of the UCO with associated teaching activity. Our biomedical re- search focuses on acute and chronic hepatocellular injury, hepatocarcinoma and liver transplants, with special empha- sis on post-translational modifications of the proteome as a consequence of oxidative stress (reactive oxygen species, ROS) and nitrosative stress (reactive nitrogen species, RNS) in eukaryotic cells (hepatocytes and yeasts). The intra- cellular cytoprotection signal for molecules of various antioxidants (N-acetylcysteine, ?-tocopherol) or cellular redox state regulators (redoxins) have been characterized in models of cellular injury. The mitochondrial dysfunction caused by redox imbalance is at the root of a large number of pathologies. The group of proteins from the family of cellular and mitochondrial redoxinas plays a major part in antioxidant defence, the maintenance of thiol systems and the inte- raction between reduced glutathione, ROS and RNS. For this purpose, normal and chimeric mutants and recombinant proteins are produced using techniques of molecular biology and in vitro characterization; and (second generation) targeted proteomics are carried out using biochemical analysis techniques.

The group’s proven experience in the analysis of post-translational modifications is employed in the identification of biomarkers for hepatocellular carcinoma detection and diagnosis using proteomic analysis tools. In the area of liver transplants, we have identified the cytoprotection mechanisms mediated by cardiotrophin-1 in the preservation injury in liver transplantation developed in experimental animals (rats and “mini-pigs”). In addition, the clinical group is invol- ved in the development of a large number of phase II, III and IV clinical trials in the areas of viral hepatitis (boceprevir), hepatocellular carcinoma (sorafenib), liver cirrhosis (satavaptan), acute liver failure (bioartificial liver, MARS) and liver transplantation (immunosuppression strategies).

Keywords

Reactive oxygen species, nitric oxide, antioxidants, redoxins, proteomics, apoptosis, necrosis, hepatocytes, yeast, mitochondria, liver cancer, biomarkers, liver transplantation, cirrhosis, viral hepatitis, acute and chronic liver failure