It is known by professionals since many years that chronic stress is apparently linked to chromosomal impairment. Now, Duke University scientists, have seemingly uncovered a mechanism that puts forth a validation for stress response with respect to DNA damage.
In the research conducted, mice were administered adrenaline-like compound that seems to function through a receptor known as the beta adrenergic receptor. The team found that this prototype of chronic stress boosts specific biological pathways that are deemed to collect 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. 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,” expressed senior author Robert J. Lefkowitz, MD, James B. Duke Professor of Medicine and Biochemistry and a Howard Hughes Medical Institute (HHMI) investigator at Duke University Medical Center.
P53 is supposedly a protein that suppresses tumor and is regarded as a helper of the genome by prohibiting genomic abnormalities. The research unfolded that chronic stress may result in persistent decrease of p53 levels. The analysts formed a hypothesis stating that this could be the cause of chromosomal abnormalities observed in the severely stressed mice.
Initial studies showed that G-protein-coupled receptors (GPCRs), like the beta adrenergic receptors are targeted by many commercially available drugs inclusive of beta blockers for heart disease, antihistamines and ulcer medications. This research focuses on the beta-arrestin pathway arising from the GPCRs. Presently, the investigators found a molecular system that seemed to instigate DNA harm. This was possibly done by the G-protein and the beta-arrestin pathways acting through this mechanism to result in the aforesaid harm.
As per the outcomes, introducing an adrenaline-like compound for a span of 4 weeks in the mice appeared to cause deterioration of p53, whose levels were eventually less over time. Moreover, mice which were devoid of beta-arrestin 1 apparently did not face DNA damage. This loss of beta-arrestin 1 probably caused the cellular levels of p53 in the thymus to become stable. The latter is an organ associated with responsiveness to chronic stress. It also seems to stabilize the cellular levels of p53 in the testes, which is the portion when paternal stress is touted to influence the child’s genome. Lefkowitz has plans of expanding the research by analyzing mice that are placed under the effect of restrained stress to know if physical reactions also result in DNA damage.
The paper was published in the August 21 online issue of Nature.