Navigation Links
Scripps Research scientists help pinpoint cause of stress-related DNA damage

JUPITER, FL, August 22, 2011 Working closely with a team of researchers from Duke University, scientists from the Florida campus of The Scripps Research Institute have helped identify a molecular pathway that plays a key role in stress-related damage to the genome, the entirety of an organism's hereditary information.

The new findings, published in the journal Nature on August 21, 2011, could not only explain the development of certain human disorders, they could also offer a potential model for prevention and therapy.

While the human mind and body are built to respond to stressthe well-known "fight or flight" response, which lasts only a few minutes and raises heart rate and blood glucose levelsthe response itself can cause significant damage if maintained over long periods of time.

When stress becomes chronic, this natural response can lead to a number of disease-related symptoms including peptic ulcers and cardiovascular disorders. To make matters worse, evidence indicates that chronic stress eventually leads to DNA damage, which in turn can result in various neuropsychiatric conditions, miscarriages, cancer, and even aging itself.

Until the new study, however, exactly how chronic stress wreaks havoc on DNA was basically unknown.

"Precisely how chronic stress leads to DNA damage is not fully understood," said Derek Duckett, associate scientific director of the Translational Research Institute at Scripps Florida. "Our research now outlines a novel mechanism highlighting β-arrestin-1 as an important player."

The long-term effects of these stress hormones on DNA damage identified in the study represent a conceptual as well as a tangible advance, according to Robert J. Lefkowitz, a Duke University professor of medicine who led the study.

Since stress is not time-limited and can be sustained over months or even years, it is well appreciated that persistent stress may have adverse effects for the individual. These new findings not only uncover a novel pathway, but also have important practical implications.

"Our results provide a possible mechanistic basis for several recent reports suggesting that significant risk reductions for diseases such as prostate cancer, lung adenocarcinoma, and Alzheimer's disease may be associated with blockade of this particular stress-response pathway by beta blockers," Leftkowitz said. "Although there are most likely numerous pathways involved in the onset of stress-related diseases, our results raise the possibility that such therapies might reduce some of the deleterious DNA-damaging consequences of long-term stress in humans."

A Newly Discovered Mechanism

The newly uncovered mechanism involves β-arrestin-1proteins, β2-adrenoreceptors (β2ARs), and the catecholamines, the classic fight-or-flight hormones released during times of stressadrenaline, noradrenaline, and dopamine. Arrestin proteins are involved in modifying the cell's response to neurotransmitters, hormones, and sensory signals; adrenoceptors respond to the catecholamines noradrenaline and adrenaline.

Under stress, the hormone adrenaline stimulates β2ARs expressed throughout the body, including sex cells and embryos. Through a series of complex chemical reactions, the activated receptors recruit β-arrestin-1, creating a signaling pathway that leads to catecholamine-induced degradation of the tumor suppressor protein p53, sometimes described as "the guardian of the genome."

The new findings also suggest that this degradation of p53 leads to chromosome rearrangement and a build-up of DNA damage both in normal and sex cells. These types of abnormalities are the primary cause of miscarriages, congenital defects, and mental retardation, the study noted.


Contact: Eric Sauter
Scripps Research Institute

Related biology news :

1. Scripps research team solves structure of beneficial virus
2. Scripps research team sheds light on immune system suppression
3. Scripps Florida scientists awarded $1.5M to fight major water and food parasites
4. Scripps research scientists identify compounds for stem-cell production from adult cells
5. Scripps research scientists identify blood component that turns bacteria virulent
6. Scripps research team defines new painkilling chemical pathway
7. Dolphin population stunted by fishing activities, Scripps/NOAA study finds
8. Scripps Research scientists shed light on how DNA is unwound so that its code can be read
9. Scripps scientists develop first examples of RNA that replicates itself indefinitely
10. Scripps scientists create first crystal structure of an intermediate particle in virus assembly
11. Historical photographs expose decline in Floridas reef fish, new Scripps study finds
Post Your Comments:
(Date:4/15/2016)... -- Research and Markets has announced the ...  report to their offering.  ,      ... gait biometrics market is expected to grow at ... Gait analysis generates multiple variables such ... compute factors that are not or cannot be ...
(Date:4/13/2016)... 13, 2016  IMPOWER physicians supporting Medicaid patients in ... new clinical standard in telehealth thanks to a new ... higi platform, IMPOWER patients can routinely track key health ... mass index, and, when they opt in, share them ... to a local retail location at no cost. By ...
(Date:3/31/2016)... , March 31, 2016  Genomics firm Nabsys ... founding CEO, Barrett Bready , M.D., who returned ... of the original technical leadership team, including Chief Technology ... of Product Development, Steve Nurnberg and Vice President of ... to the company. Dr. Bready served as ...
Breaking Biology News(10 mins):
(Date:6/23/2016)... June 23, 2016 Houston Methodist Willowbrook ... Cy-Fair Sports Association to serve as their official ... Houston Methodist Willowbrook will provide sponsorship support, athletic ... with association coaches, volunteers, athletes and families. ... Cy-Fair Sports Association and to bring Houston Methodist ...
(Date:6/23/2016)... 23, 2016   EpiBiome , a precision microbiome ... in debt financing from Silicon Valley Bank (SVB). The ... to advance its drug development efforts, as well as ... "SVB has been an incredible strategic partner to ... traditional bank would provide," said Dr. Aeron Tynes ...
(Date:6/23/2016)... Apellis Pharmaceuticals, Inc. today announced positive ... its complement C3 inhibitor, APL-2. The trials were ... studies designed to assess the safety, tolerability, pharmacokinetics ... healthy adult volunteers. Forty subjects were ... dose (ranging from 45 to 1,440mg) or repeated ...
(Date:6/23/2016)... ... June 23, 2016 , ... ... the Pennsylvania Convention Center and will showcase its product’s latest features from June ... be presenting a scientific poster on Disrupting Clinical Trials in The Cloud during ...
Breaking Biology Technology: