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A team from the Consejo Superior de Investigaciones Científicas (CSIC) has identified a new mechanism to protect the liver from acute liver damage characteristic of the different types of hepatitis and poisoning by normal consumption of drugs or medicines. The investigation, which is published in Hepatology, focuses on protein S6 kinase 1. According to the authors, its inhibition could represent a potential therapeutic target against these symptoms.

CSIC researcher Angela Martinez Valverde, Instituto de Investigaciones Biomédicas Alberto Sols (CSIC) in Madrid, directed this research with the collaboration of researchers from the University of Cincinnati, USA.

The results of the work, tested in cellular and animal models show that if it inhibits the action of the protein S6 kinase 1 (S6K1) in hepatocytes, cells that play a large part of the functions of the liver, protects against apoptosis (programmed cell death) induced by activation of cell death receptors TNF-R1 and Fas.

These findings, says Martinez Valverde, suggesting that the inhibition of S6K1 could be useful therapeutics to alleviate the acute liver damage. The work also provides useful information to advance the development of antitumor therapies based on inhibiting the mTOR protein.

Multiple studies have proven its usefulness in diseases such as liver cancer and, at present, inhibitors of this protein, as rampamicina, are in various stages of clinical testing. However, as explained by the CSIC's research, the emergence of resistance to these drugs has highlighted the need to delve into the molecular mechanisms responsible for this phenomenon. "

The identification of the molecular mechanism by which the inhibition of S6K1 pathways activated maintains survival of hepatocytes provided by this study could explain the emergence of resistance to treatment with mTOR inhibitors, the authors say. "By not responding to stimuli of cell death, S6K1-deficient hepatocytes show a behavior similar to that shown in cells resistant to the antineoplastic effects of inhibitors of mTOR," says Martínez Valverde.

In his view, to improve the effectiveness of anticancer drug based on inhibition of mTOR would require a combination with drugs that prevent the sustained activation of cell survival pathways, inhibition of S6K1.