Navigation Links
Free radical cell death switch identified

"A common molecular denominator in aging and many age-related diseases is oxidative stress," says the study's lead author Azad Bonni, MD, PhD, HMS associate professor of pathology. The skin of a bitten apple will brown because of its exposure to air, and in some ways that is a good metaphor for the damage that oxidative stress is causing to neurons and other types of cells over time.

Humans and other organisms depend on oxygen to produce the energy required for cells to carry out their normal functions. A cell's engine, the mitochondria, converts oxygen into energy. But this process also leaves a kind of exhaust product known as free radicals. When free radicals are not destroyed by antioxidants, they create oxidative stress. As the body ages, it produces more and more free radicals and its own antioxidants are unable to fight this process, which results in the generation of highly reactive oxygen molecules that inflict cellular damage by reacting with biomolecules including DNA, proteins, and lipids. A lifetime of oxidative stress leads to general cellular deterioration associated with aging and degenerative diseases.

How the oxidative-stress signals trigger these profound effects in cells has remained unclear. But Bonni and his research team, including Maria Lehtinen, a graduate student in the HMS program in neuroscience, and Zengqiang Yuan, PhD, an HMS research fellow in pathology, in collaboration with Keith Blackwell, MD, PhD, HMS associate professor of pathology, have now defined how a molecular chain-of-events links oxidative-stress signals to cell death in brain neurons.

In the course of investigating the mechanisms of cell death in neurons from rat brain, the team focused their attention on the function of a protein called MST, which had been previously implicated in cell death. They found that exposure of brain neurons to oxidative-stress signals stimulates the activity of MST, and once activated, MST instructs neurons to die. The researchers also found a tight link between MST and another family of molecules called FOXO proteins. FOXO proteins turn on genes in the nucleus, the command center of the cell. Once stimulated by oxidative stress, MST acts in its capacity as an enzyme to modify and thereby activate the FOXO proteins, instructing the FOXO proteins to move from the periphery of the cell into the nucleus of neurons. Once in the nucleus, the FOXO proteins were found to turn on genes that commit neurons to programmed death.

The discovery of the MST-FOXO biochemical switch mechanism fills a gap in our understanding of how oxidative stress elicits biological responses in neurons, and may include besides cell death, neuronal dysfunction and neuronal recovery. Since oxidative stress in neurons and other cells in the body contribute to tissue damage in a variety of disorders, including stroke, ischemic heart disease, neurodegenerative diseases, and diabetes, identification of the MST-FOXO switch mechanism could provide potential new targets for the diagnosis and treatment of many common age-associated diseases.


'"/>

Source:Harvard Medical School


Related biology news :

1. Researchers extend mouse lifespan by protecting against free radicals
2. A radical solution for environmental pollution
3. Free-radical busting antioxidants might not promote healthy hearts
4. Delft water-purification method promises radical improvement
5. Combination therapy boosts effectiveness of telomere-directed cancer cell death
6. Enzyme allows B cells to resist death, leading to leukemia
7. Critical role in programmed cell death identified
8. A comprehensive response to HIV could prevent 10 million AIDS deaths in Africa by 2020
9. The death of a very special chimpanzee
10. The very unexpected life and death of a leukemic cell
11. Solutions that reduce death of marine life reeled in by International Smart Gear Competition
Post Your Comments:
*Name:
*Comment:
*Email:


(Date:3/23/2016)... March 23, 2016 ... Sicherheit Gesichts- und Stimmerkennung mit Passwörtern ... (NASDAQ: MESG ), ein führender Anbieter ... Unternehmen mit SpeechPro zusammenarbeitet, um erstmals dessen ... wird die Möglichkeit angeboten, im Rahmen mobiler ...
(Date:3/22/2016)... OTTAWA, Ontario , PROVO ... 2016 Newborn Screening Ontario (NSO), which operates ... for molecular testing, and Tute Genomics and ... process management technology respectively, today announced the launch of ... new next-generation sequencing (NGS) testing panel. ...
(Date:3/18/2016)... 2016 --> --> ... Manned & Unmanned Vehicles, Physical infrastructure and Perimeter Surveillance & ... the border security market and the continuing migration crisis in ... Europe has led visiongain to publish this unique ... --> defence & security companies in the border ...
Breaking Biology News(10 mins):
(Date:6/23/2016)... ... June 23, 2016 , ... UAS LifeSciences, ... launch of their brand, UP4™ Probiotics, into Target stores nationwide. The company, which ... to add Target to its list of well-respected retailers. This list includes such ...
(Date:6/23/2016)... Houston Methodist Willowbrook Hospital has signed ... to serve as their official health care provider. ... will provide sponsorship support, athletic training services, and ... volunteers, athletes and families. "We are ... and to bring Houston Methodist quality services and ...
(Date:6/23/2016)... --  EpiBiome , a precision microbiome engineering company, today ... from Silicon Valley Bank (SVB). The financing will allow ... drug development efforts, as well as purchase additional lab ... been an incredible strategic partner to us – one ... provide," said Dr. Aeron Tynes Hammack , EpiBiome,s ...
(Date:6/23/2016)... June 23, 2016 Apellis Pharmaceuticals, Inc. ... clinical trials of its complement C3 inhibitor, APL-2. ... multiple ascending dose studies designed to assess the ... subcutaneous injection in healthy adult volunteers. ... as a single dose (ranging from 45 to ...
Breaking Biology Technology: