Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Oxidative Stress: Mechanism of Cell Death Clarified

03.09.2008
Dr. Marcus Conrad of the Institute of Clinical Molecular Biology and Tumor Genetics at the Helmholtz Zentrum München has decrypted the molecular mechanism through which the death of cells is caused by oxidative stress.

This knowledge opens novel perspectives to systematically explore the benefit of targeted therapeutic interventions in the cure of ageing and stress-related degenerative diseases.

Life processes in cells require a reducing environment that needs to be sustained with the help of a large number of antioxidative enzymes. This may sound abstract and incomprehensible, but everyone knows the phenomenon that a piece of cut apple or a piece of cut meat changes colour quickly and deteriorates, because the oxygen in the air produces chemical reactions in the tissues (oxidation of biomolecules).

If the equilibrium in the organism moves towards oxidative processes, then this is known as oxidative stress. Oxidative stress, for instance, is associated with the aging of body cells. Furthermore, a strong accumulation of reactive oxygen species (ROS) along with drops in cellular concentrations of glutathione, (GSH), the major antioxidant produced by the body, is well known as a common cause of acute and chronic degenerative diseases, such as, arteriosclerosis, diabetes, stroke, Alzheimer's and Parkinson's diseases.

"To investigate the molecular function of the cellular reducing agent GSH in the metabolic pathway of cell death triggered by oxidative stress, mice and cells were generated that specifically lack glutathione peroxidase 4 (GPx4), which is emerging as one of the most important GSH dependent enzymes", explains Marcus Conrad. The induced inactivation of GPx4 caused massive oxidation of lipids and eventually cell death. A similar phenotype could be observed when intracellular GSH was removed from wild-type cells by a chemical inhibitor of GSH biosynthesis.

Interestingly enough, this cell death could be completely prevented by Vitamin E, but not by water-soluble antioxidants. Since the oxidation of fatty acids in this cell death pathway, was of paramount importance, multiple studies were performed to describe, in greater detail, the source and nature of lipid peroxides.

Pharmacological and reverse genetic analyses showed that lipid peroxides in GPx4-depleted cells do not appear by coincidence, but accumulate due to increased activity of a specific enzyme of the arachidonic acid metabolism, the 12/15-lipoxygenase. Activation of apoptosis inducing factor (AIF), evidenced by its relocation from mitochondria to the cell nucleus, was identified as another important event in this signaling cascade.

The fact that oxidative stress is a major inducer of cell death is a well accepted current model. Until now however, the source and nature of the reactive oxygen species has remained obscure, as have questions concerning the way they act. Marcus Conrad: "So far, it was assumed that oxidative stress is detrimental to cells by unspecific oxidation of many essential biomolecules, such as proteins and lipids. That is why we were amazed to find that in cells lacking either glutathione or glutathione peroxidase 4, a distinctive signaling pathway is engaged, which causes cell death. The data represent the first molecular analyses of a redox-regulated signaling pathway, describing how oxidative stress is recognized in the body and translated into cell death".

Since this cell death cascade can be interrupted at any single stage with the help of drugs, this pathway harbors promising targets for therapeutic intervention to mitigate the deleterious effects of oxidative stress in complex degenerative human diseases.

Michael van den Heuvel | alfa
Further information:
http://www.helmholtz-muenchen.de

More articles from Life Sciences:

nachricht Ion treatments for cardiac arrhythmia — Non-invasive alternative to catheter-based surgery
20.01.2017 | GSI Helmholtzzentrum für Schwerionenforschung GmbH

nachricht Seeking structure with metagenome sequences
20.01.2017 | DOE/Joint Genome Institute

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Traffic jam in empty space

New success for Konstanz physicists in studying the quantum vacuum

An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...

Im Focus: How gut bacteria can make us ill

HZI researchers decipher infection mechanisms of Yersinia and immune responses of the host

Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...

Im Focus: Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.

While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...

Im Focus: Studying fundamental particles in materials

Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales

Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...

Im Focus: Designing Architecture with Solar Building Envelopes

Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.

As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Sustainable Water use in Agriculture in Eastern Europe and Central Asia

19.01.2017 | Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

 
Latest News

Helmholtz International Fellow Award for Sarah Amalia Teichmann

20.01.2017 | Awards Funding

An innovative high-performance material: biofibers made from green lacewing silk

20.01.2017 | Materials Sciences

Ion treatments for cardiac arrhythmia — Non-invasive alternative to catheter-based surgery

20.01.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>