Science Doing: Chronic stress alters gene activity in immune cells and oxidative stress detection tools

Chronic stress' effects can be traced to your genes

Researchers say repeated stress that triggers the sympathetic nervous system can lead to inflammation that is linked to many health problems.

A bad boss can cripple your immune system
"So what this suggests is that if you're working for a really bad boss over a long period of time, that experience may play out at the level of gene expression in your immune system."

Last Updated: Wednesday, November 06, 2013, 16:02

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Washington: A new study has showed that chronic stress alters gene activity in immune cells
before they reach the bloodstream.

With these changes,
the cells are primed to fight an infection or trauma that doesn't actually exist,
leading to an overabundance of the inflammation that is linked to many health problems.

Ohio State University scientists made and their colleagues from other institutions, testing blood samples from humans living in poor socioeconomic conditions, found that similarly primed immune cells were present in these chronically stressed people as well.

Co-lead author John Sheridan, professor of oral biology in the College of Dentistry and associate director of Ohio State's Institute for Behavioral Medicine Research (IBMR),sa di that the cells share many of the same characteristics in terms of their response to stress.

He said that there is a stress-induced alteration in the bone marrow in both our mouse model and in chronically stressed humans that selects for a cell that's going to be pro-inflammatory.

Sheridan and colleagues have been studying the same mouse model for a decade to reveal how chronic stress - and specifically stress associated with social defeat - changes the brain and body in ways that affect behavior and health.

The mice are repeatedly subjected to stress that might resemble a person's response to persistent life stressors. In this model, male mice living together are given time to establish a hierarchy, and then an aggressive male is added to the group for two hours at a time.

This elicits a "fight or flight" response in the resident mice as they are repeatedly defeated by the intruder.

Under normal conditions, the bone marrow in animals and humans is making and releasing billions of red blood cells every day, as well as a variety of white blood cells that constitute the immune system.

In this work, the researchers compared cells circulating in the blood of mice that had experienced repeated social defeat to cells from control mice that were not stressed. The stressed mice had an average fourfold increase in the frequency of immune cells in their blood and spleen compared to the normal mice.

#The study has been published in the journal Proceedings of the National Academy of Sciences.

#This work was supported by the National Institutes of Health; the Mind, Body, Brain and Health Initiative of the John D. and Catherine T. MacArthur Foundation; the British Columbia Ministry of Child and Family Development via the Human Early Learning Partnership; and the Allergy, Genes and Environment Research Network.

Additional co-authors are Erica Sloan of UCLA and the Monash Institute of Pharmaceutical Sciences in Australia; Michael Bailey (associate professor of oral biology) and Brenda Reader of Ohio State's IBMR; Jesusa Arevalo of UCLA; Gregory Miller and Edith Chen of Northwestern University; and Michael Kobor of the University of British Columbia.(http://www.eurekalert.org/pub_releases/2013-11/osu-eoc110513.php)

Oxidative stress

is considered to be involved in

a multitude of pathogenic processes

and is also implicated in the process of aging.

Generation of reactive oxygen species (ROS) is inevitable for aerobic organisms and, in healthy cells, occurs at a controlled rate. Under conditions of oxidative stress, ROS production is dramatically increased, resulting in subsequent alteration of membrane lipids, proteins, and nucleic acids. Oxidative damage of these biomolecules is associated with aging as well as a variety of pathological events, including atherosclerosis, carcinogenesis, ischemia reperfusion injury, and neurodegenerative disorders.

oxidative stress detection

courtesy share: http://www.invitrogen.com

Tools to track different parameters in oxidative stress:
(These tools use platforms such as fluorescence microscopy, flow cytometry, or microplate analysis.)

Generalized oxidative stress: Oxidative stress results from an imbalance in the production of reactive oxygen species (ROS) and the ability of the cell to scavenge them. ROS react with nucleic acids, proteins and lipids causing cell and tissue damage and can be measured using selective or general indicators.

Detection of oxidative stress

courtesy share: http://www.invitrogen.com

Lipid peroxidation: Lipid peroxidation is the oxidative degradation of lipids. Reactive oxygen species are the major initiators of lipid peroxidation and membrane bound polyunsaturated fatty acids like arachidonic acid and linoleic acid are their major targets. The byproducts of lipid peroxidation cause direct damage to cell membranes. They also form protein adducts resulting in cell and tissue damage. Lipid peroxidation is implicated in many human diseases including diabetes and cardiovascular disease.

Detection of lipid peroxidation

courtesy share: http://www.invitrogen.com

Selective ROS detection: Superoxide, peroxyl radical, hydrogen peroxide, hydroxyl radical and peroxynitrite are some examples of ROS that react with nucleic acids, proteins and lipids and result in cell and tissue damage. Certain ROS have been implicated in various human diseases including cancer, cardiovascular disease, neurodegenerative disease and aging.

Detection of superoxide in live cells

courtesy share: http://www.invitrogen.com

Glutathione levels: Reduced glutathione also known as GSH is a major thiol bound to proteins. Protein thiols including GSH play an important role in determining the redox status of cells. Therefore, detection of reduced GSH levels is a useful indication of redox potential and a cell's ability to prevent oxidative stress.