Researchers look at role of oxidative stress in human diseases

Oxidative stress is known to underlie many human diseases including atherosclerosis, Parkinson's disease and Alzheimer's disease.

A team of scientists from Boston College has found a means to discover more about what role oxidative stress plays in the development of diseases by studying it at the sub-cellular level.

Available information about the oxidative stress response has come primarily from studies using reactive oxygen species (ROS) with ill-defined locations within the cell, according to the researchers. Thus, they say, existing models do not account for possible differences between stress originating within particular regions of the cell.

Through the use of novel synthetic intracellular targeting molecules that contain oxygen species-generating compounds that cause oxidative stress, the Boston College researchers have targeted specific locations within the cell — notably the nucleus and mitochondrion — and observed how these molecules interact with nucleic acids (DNA). This will make it easier to determine what parts of a cell are most likely to combat the effects of oxidative stress, and which are weaker, according to the researchers.

That knowledge, in turn, could someday lead to the development of toxic agents that could be used, for example, to attack cancer at the sub-cellular level.

The research, published in the most recent issue of the journal Chemistry & Biology, demonstrates the value of interdepartmental and interdisciplinary collaborations, say the investigators, a trend which is becoming a hallmark of Boston College's natural science programs.

"This experience is an illustration of what can happen when you have an environment where chemists and biologists continually encounter each other, formally and informally. Conversations start, ideas are exchanged and progress is made rapidly; these historically separate disciplines can get together to share observations and work together," said Boston College Professor of Biology Thomas Chiles, a study co-author whose lab was involved in the research.

Chiles says the collaboration began a few years ago when he and Professor Shana Kelley — then a faculty member in the Boston College Chemistry Department now at the University of Toronto — were serving on a committee together. She described her research to Chiles, and the two scientists began exchanging ideas and sharing lab resources and staff to work on the project.

Kelley had designed highly innovative chemical probes to target specific locations within the cell, Chiles explains. "Once inside, she knew the compounds were killing the cell, but she needed another perspective, because she was dealing with questions of a biological nature. How were these compounds killing the cell" How does a cell survive oxidative stress"

"Past research on oxidative stress focused on the cell as a whole, so it was difficult to ascertain exactly what was happening at the molecular level. But with these compounds developed through Shana's lab, we can begin to understand the specifics of the cell's response to oxidative stress.

"The next step is to look at whether the changes occurring within the cell are its response to the oxidative stress caused by the compounds, or if the compounds themselves are triggering the changes."

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