Navigation Links
At last, a reason why stress causes DNA damage
Date:8/21/2011

DURHAM, N.C. For years, researchers have published papers that associate chronic stress with chromosomal damage.

Now researchers at Duke University Medical Center have discovered a mechanism that helps to explain the stress response in terms of DNA damage.

"We believe this paper is the first to propose a specific mechanism through which a hallmark of chronic stress, elevated adrenaline, could eventually cause DNA damage that is detectable," said senior author Robert J. Lefkowitz, M.D., James B. Duke Professor of Medicine and Biochemistry and a Howard Hughes Medical Institute (HHMI) investigator at Duke University Medical Center.

The paper was published in the Aug. 21 online issue of Nature.

In the study, mice were infused with an adrenaline-like compound that works through a receptor called the beta adrenergic receptor that Lefkowitz has studied for many years. The scientists found that this model of chronic stress triggered certain biological pathways that ultimately resulted in accumulation of DNA damage.

"This could give us a plausible explanation of how chronic stress may lead to a variety of human conditions and disorders, which range from merely cosmetic, like graying hair, to life-threatening disorders like malignancies," Lefkowitz said.

P53 is a tumor suppressor protein and is considered a "guardian of the genome" one that prevents genomic abnormalities.

"The study showed that chronic stress leads to prolonged lowering of p53 levels," said Makoto Hara, Ph.D., a postdoctoral fellow in the Lefkowitz laboratory. "We hypothesize that this is the reason for the chromosomal irregularities we found in these chronically stressed mice."

Lefkowitz earlier had proved the existence of isolated, and characterized the G-protein-coupled receptors (GPCRs) such as the beta adrenergic receptor. These receptors, which are located on the surface of the membranes that surround cells, are the targets of almost half of the drugs on the market today, including beta blockers for heart disease, antihistamines and ulcer medications.

Now he is continuing studies along another pathway,stemming from the GPCRs, that was discovered in his lab, which is known as the beta-arrestin pathway. At first, the theory was that beta-arrestin proteins turned off or desensitized the G-protein pathways, but evidence is accumulating that these proteins are also responsible for causing certain biochemical activities in their own right.

In the current study, the scientists found a molecular mechanism through which adrenaline-like compounds acted through both G-protein and the beta-arrestin pathways to trigger DNA damage.

The Nature publication showed that the infusion of an adrenaline-like compound for four weeks in the mice caused degradation of p53, which was present in lower levels over time.

The study also showed that the DNA damage was prevented in mice lacking beta-arrestin 1. Loss of beta-arrestin 1 stabilized cellular levels of p53 both in the thymus, an organ that strongly responds to acute or chronic stress, and in the testes, where paternal stress might affect an offspring's genome.

Future studies planned by the Lefkowitz laboratory include studying mice that are placed under stress (restrained), thus creating their own adrenaline or stress reaction to learn whether the physical reactions of stress, rather than an influx of adrenaline in the lab as was done in the current study, also leads to accumulation of DNA damage.


'/>"/>

Contact: Mary Jane Gore
mary.gore@duke.edu
919-660-1309
Duke University Medical Center
Source:Eurekalert

Related biology news :

1. Happy guys finish last, says new study on sexual attractiveness
2. Another reason to drink a nice cup of shade-grown joe
3. LSUHSC public health researcher finds reason for weight gain
4. 100 reasons to change the way we think about genetics
5. Babies and sleep: Another reason to love naps
6. Black mothers cite lack of desire as top reasons for not breastfeeding
7. Study: Reasonable quantities of red pepper may help curb appetite
8. Yale researchers pinpoint reasons for dramatic rise in cesarean births
9. College scientist cites enlarged skeletal muscles as reason birds exist
10. University professor stresses links between US Navy sonar and whale strandings
11. Exposing chicks to maternal stress leads to long-term reproductive success
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:3/30/2017)... , March 30, 2017 The research ... system for three-dimensional (3D) fingerprint identification by adopting ground breaking 3D ... a new realm of speed and accuracy for use in identification, ... an affordable cost. ... ...
(Date:3/28/2017)... , March 28, 2017 ... Biometrics), Hardware (Camera, Monitors, Servers, Storage Devices), Software (Video ... and Region - Global Forecast to 2022", published by ... in 2016 and is projected to reach USD 75.64 ... 2017 and 2022. The base year considered for the ...
(Date:3/24/2017)... Research and Markets has announced the addition of the "Global ... to 2025" report to their offering. ... The Global Biometric Vehicle Access System Market ... the next decade to reach approximately $1,580 million by 2025. ... for all the given segments on global as well as regional ...
Breaking Biology News(10 mins):
(Date:10/11/2017)... ... 2017 , ... A new study published in Fertility and ... in vitro fertilization (IVF) transfer cycles. The multi-center matched cohort study ... comparing the results from the fresh and frozen transfer cohorts, the authors of ...
(Date:10/10/2017)... ... October 10, 2017 , ... For the second time in ... STEM Mentoring Award. Representatives of the FirstHand program travelled to Washington, D.C. Tuesday, ... , US2020’s mission is to change the trajectory of STEM education in America ...
(Date:10/10/2017)... CALIFORNIA (PRWEB) , ... October 10, 2017 , ... ... technological innovation and business process optimization firm for the life sciences and healthcare ... BoxWorks conference in San Francisco. , The presentation, “Automating GxP Validation for ...
(Date:10/9/2017)... (PRWEB) , ... October 09, 2017 , ... At its ... Dr. Christopher Stubbs, a professor in Harvard University’s Departments of Physics and Astronomy, has ... was a member of the winning team for the 2015 Breakthrough Prize in Fundamental ...
Breaking Biology Technology: