Navigation Links
Oxidative stress: Mechanism of cell death clarified
Date:9/3/2008

This press release is available in German.

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.


'/>"/>

Contact: Heinz-Jrg Haury
presse@helmholtz-muenchen.de
49-893-187-2460
Helmholtz Zentrum Mnchen - German Research Center for Environmental Health
Source:Eurekalert

Related biology news :

1. Boston College profs study oxidative stress subcellular to discover its role in diseases
2. Researchers discover cells quality control mechanism
3. Discovery of a mechanism that regulates cell movement
4. UCLA study identifies mechanism behind mind-body connection
5. UGA researchers discover mechanism that explains how cancer enzyme winds up on ends of chromosomes
6. Scientists reveal the key mechanisms for affinity between transient binding proteins
7. A single mechanism for hypertension, insulin resistance and immune suppression
8. Mechanism and function of humor identified by new evolutionary theory
9. LIAI researchers discover new cellular mechanism that will significantly advance vaccine development
10. Mechanism explains link between apolipoprotein E and Alzheimers disease
11. Jefferson receives $11.6M NIH grant to study novel mechanisms of heart failure
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:4/5/2017)... LONDON , April 4, 2017 KEY ... is anticipated to expand at a CAGR of 25.76% ... neurodegenerative diseases is the primary factor for the growth ... full report: https://www.reportbuyer.com/product/4807905/ MARKET INSIGHTS The ... of product, technology, application, and geography. The stem cell ...
(Date:3/30/2017)... , March 30, 2017  On April 6-7, 2017, ... the Genome hackathon at Microsoft,s headquarters in ... competition will focus on developing health and wellness apps ... Hack the Genome is the first hackathon ... The world,s largest companies in the genomics, tech and ...
(Date:3/29/2017)... , March 29, 2017  higi, the health IT ... North America , today announced a ... the acquisition of EveryMove. The new investment and acquisition ... of tools to transform population health activities through the ... data. higi collects and secures data today ...
Breaking Biology News(10 mins):
(Date:8/16/2017)... Ca (PRWEB) , ... August 16, 2017 , ... ... by changing into a different cell type. Many treatments for specific cancers, such ... prominent example of targeted treatment is androgen deprivation therapy for advanced prostate cancer. ...
(Date:8/16/2017)... (PRWEB) , ... August 16, 2017 , ... ... beneficial microbe delivery system, announced it has secured $2M in funding from an ... City Angels, Carmen Innovations, and SVG Thrive Fund. With this investment, 3Bar is ...
(Date:8/16/2017)... WAKEFIELD, Mass. , Aug. 16, 2017  This year,s edition of ... global leader in life sciences workforce solutions, has made the list for ... Inc. 5000 recognizes the nation,s fastest-growing private companies based on a set ... Fast 50, which includes the fastest-growing companies in the Bay ... Inc. 5000 ...
(Date:8/15/2017)... 15, 2017 After spending the past two years building ... data collection, GeneFo now offers this platform to healthcare stakeholders (hospitals, ... support, adherence, and data collection vis a vis their members, under ... successful launch of this offer. ... GeneFo ...
Breaking Biology Technology: