New target to improve liver antioxidant defenses

New target to improve liver antioxidant defenses https://i2.wp.com/www.eresviral.com/wp-content/uploads/2018/11/Nueva-diana-para-mejorar-las-defensas-antioxidantes-hepáticas.jpg?fit=195%2C146&ssl=1

New target to improve liver antioxidant defenses







New advances in the study of PASK suggest that the deficiency of this protein could promote antioxidant mechanisms against oxidative stress in the liver. Researchers from the CIBER Diabetes and Metabolic Associated Diseases (CIBERDEM) led by Elvira Álvarez and Carmen Sanz at the Complutense University of Madrid and the Sanitary Research Institute of the San Carlos Clinical Hospital in Madrid (Spain), reveal how these hepatic antioxidant mechanisms are improved when the PASK protein is blocked. The results have been published in Scientific Reports.



"By blocking the PASK protein in mice, we have observed how antioxidant defenses are increased, improving the response to possible damage and avoiding the generation of oxidative stress," the researchers explain. Therefore, added "the stimulation of antioxidant responses could be useful to prevent or treat liver diseases such as hepatitis, cirrhosis and fatty liver."



Metabolic dysfunction in the liver is the cause of numerous pathologies associated with an altered redox state. The new results suggest that the PASK protein can act as a driver of oxidative stress and be key in the antioxidant response. Potentially, the researchers consider, "could be a good therapeutic target to prevent and treat certain liver pathologies."



The cells, in their normal functioning, produce free radicals. These molecules, in excessive amounts, are toxic and cause damage to DNA and other cellular components. The excessive accumulation of these is what is called oxidative stress and is harmful to cells.







Authors of the study. (Photo: CIBER)



Oxidative stress is associated with diseases such as diabetes, cancer, cardiovascular disorders or neurodegenerative diseases. In this sense, the liver is an organ especially sensitive to this process. For example, alcohol consumption, hypercaloric diet, environmental pollution, heavy metals, etc. cause liver damage due to the generation of oxidative stress.



Previous research of this same group, showed how the PASK protein is key in the regulation of hepatic genes and proteins involved in the detection and metabolism of glucose, as well as in insulin signaling. Therefore, it affects the response to the nutritional changes that regulate the metabolism of glucose and lipids. Thus, PASK would be controlling the hepatic metabolism and the homeostasis of glucose and lipids throughout the body.



Previously, the researchers had already described how these mice deficient in the protein not only did not develop obesity, but that they had an improved response to insulin when they were subjected to high-fat diets.



These findings of the group led by Elvira Álvarez from CIBERDEM and the Universidad Complutense de Madrid reinforce the interest of this protein as a target to develop future treatments of the aforementioned diseases. In this sense, the group is developing lines of research and contacts that facilitate these ends. (Source: CIBER / DICYT)

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