Featured Research

from universities, journals, and other organizations

Oxidative Stress: Mechanism Of Cell Death Clarified

Date:
September 7, 2008
Source:
Helmholtz Zentrum Muenchen - German Research Centre for Environmental Health
Summary:
Scientists have 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 aging and stress-related degenerative diseases.

Dr. Marcus Conrad of the Institute of Clinical Molecular Biology and Tumor Genetics at the Helmholtz Zentrum Mόnchen 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.


Story Source:

The above story is based on materials provided by Helmholtz Zentrum Muenchen - German Research Centre for Environmental Health. Note: Materials may be edited for content and length.


Cite This Page:

Helmholtz Zentrum Muenchen - German Research Centre for Environmental Health. "Oxidative Stress: Mechanism Of Cell Death Clarified." ScienceDaily. ScienceDaily, 7 September 2008. <www.sciencedaily.com/releases/2008/09/080903075612.htm>.
Helmholtz Zentrum Muenchen - German Research Centre for Environmental Health. (2008, September 7). Oxidative Stress: Mechanism Of Cell Death Clarified. ScienceDaily. Retrieved September 30, 2014 from www.sciencedaily.com/releases/2008/09/080903075612.htm
Helmholtz Zentrum Muenchen - German Research Centre for Environmental Health. "Oxidative Stress: Mechanism Of Cell Death Clarified." ScienceDaily. www.sciencedaily.com/releases/2008/09/080903075612.htm (accessed September 30, 2014).

Share This



More Health & Medicine News

Tuesday, September 30, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

How 'Yes Means Yes' Defines Sexual Assault

How 'Yes Means Yes' Defines Sexual Assault

Newsy (Sep. 29, 2014) — Aimed at reducing sexual assaults on college campuses, California has adopted a new law changing the standard of consent for sexual activity. Video provided by Newsy
Powered by NewsLook.com
Scientists May Have Found An Early Sign Of Pancreatic Cancer

Scientists May Have Found An Early Sign Of Pancreatic Cancer

Newsy (Sep. 29, 2014) — Researchers looked at 1,500 blood samples and determined people who developed pancreatic cancer had more branched chain amino acids. Video provided by Newsy
Powered by NewsLook.com
Colo. Doctors See Cluster of Enterovirus Cases

Colo. Doctors See Cluster of Enterovirus Cases

AP (Sep. 29, 2014) — Doctors at the Children's Hospital of Colorado say they have treated over 4,000 children with serious respiratory illnesses since August. Nine of the patients have shown distinct neurological symptoms, including limb weakness. (Sept. 29) Video provided by AP
Powered by NewsLook.com
Dr.'s Unsure of Cause of Fast-Spreading Virus

Dr.'s Unsure of Cause of Fast-Spreading Virus

AP (Sep. 29, 2014) — Doctors at the Children's Hospital of Colorado say they have treated over 4,000 children with serious respiratory illnesses since August. Nine of the patients have shown distinct neurological symptoms, including limb weakness. (Sept. 29) Video provided by AP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
 
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:  

Breaking News:

Strange & Offbeat Stories

 

Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:  

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile iPhone Android Web
Follow Facebook Twitter Google+
Subscribe RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins