XML Feed for RxPG News   Add RxPG News Headlines to My Yahoo!   Javascript Syndication for RxPG News

Research Health World General
 
  Home
 
 Latest Research
 Cancer
 Psychiatry
 Genetics
 Surgery
 Aging
 Ophthalmology
 Gynaecology
 Neurosciences
 Pharmacology
 Cardiology
 Obstetrics
 Infectious Diseases
 Respiratory Medicine
 Pathology
 Endocrinology
 Immunology
 Nephrology
 Gastroenterology
 Biotechnology
 Radiology
 Dermatology
 Microbiology
 Haematology
 Dental
 ENT
 Environment
 Embryology
 Orthopedics
 Metabolism
 Anaethesia
 Paediatrics
 Public Health
 Urology
 Musculoskeletal
 Clinical Trials
 Physiology
 Biochemistry
  Proteins
 Cytology
 Traumatology
 Rheumatology
 
 Medical News
 Health
 Opinion
 Healthcare
 Professionals
 Launch
 Awards & Prizes
 
 Careers
 Medical
 Nursing
 Dental
 
 Special Topics
 Euthanasia
 Ethics
 Evolution
 Odd Medical News
 Feature
 
 World News
 Tsunami
 Epidemics
 Climate
 Business
Search

Last Updated: Aug 19th, 2006 - 22:18:38

Biochemistry Channel
subscribe to Biochemistry newsletter

Latest Research : Biochemistry

   DISCUSS   |   EMAIL   |   PRINT
MST-FOXO - Free radical cell death switch mechanism
Jun 8, 2006, 02:44, Reviewed by: Dr. Priya Saxena

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.

 
Just as humans undergo daily stress, so do our individual cells. The cellular variety, called oxidative stress, is caused by the build-up of free radicals, which over time inflict damage linked to aging and age related diseases such as Alzheimer's. Researchers at Harvard Medical School (HMS) have now defined a molecular signaling pathway by which oxidative stress triggers cell death, a finding that could pave the way for new drug targets and diagnostic strategies for age-related diseases.

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.

"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.

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.
 

- The findings are reported in the June 2 issue of Cell.
 

www.hms.harvard.edu

 
Subscribe to Biochemistry Newsletter
E-mail Address:

 

Harvard Medical School has more than 7,000 full-time faculty working in eight academic departments based at the School's Boston quadrangle or in one of 47 academic departments at 18 Harvard teaching hospitals and research institutes. Those Harvard hospitals and research institutions include Beth Israel Deaconess Medical Center, Brigham and Women's Hospital, Cambridge Health Alliance, the CBR Institute for Biomedical Research, Children's Hospital Boston, Dana-Farber Cancer Institute, Forsyth Institute, Harvard Pilgrim Health Care, Joslin Diabetes Center, Judge Baker Children's Center, Massachusetts Eye and Ear Infirmary, Massachusetts General Hospital, Massachusetts Mental Health Center, McLean Hospital, Mount Auburn Hospital, Schepens Eye Research Institute, Spaulding Rehabilitation Hospital, and VA Boston Healthcare System.

Related Biochemistry News

First major study of mammalian 'disorderly' proteins
Revolutionary New Tool to Watch Real-Time Chemical Activity in Cells
Exploring mechanics of chromatid cohesion
Shape of a Common Protein Module Munc-13 Suggests Role as Molecular Switch
MST-FOXO - Free radical cell death switch mechanism
New process to inhibit zinc finger protein, HIV NCp7
New methods of structural genomics have accelerated studies of individual proteins
Lethal Gene Mutation Key to Blocking Cholesterol Processing Uncovered
Wnt - One Signal, Multiple Pathways: Diversity Comes from the Receptor
Prostate cancer manipulates Wnts signaling proteins in bony metastasis


For any corrections of factual information, to contact the editors or to send any medical news or health news press releases, use feedback form

Top of Page

 

© Copyright 2004 onwards by RxPG Medical Solutions Private Limited
Contact Us