Surgery News

U-M scientists develop tool to probe role of oxidative stress in aging, disease

October 16, 2015

This "oxidative stress" is associated with many diseases, such as Alzheimer's, heart disease and cancer, and has been suggested to be the culprit underlying aging.

In an article published online Feb. 14 in the journal Proceedings of the National Academy of Sciences (PNAS), University of Michigan researchers led by associate professor Ursula Jakob report on a new method that allows them to observe how oxidative stress affects the major building blocks of a cell, the proteins. The new technique, called OxICAT, makes it possible to quantify the oxidation state of thousands of different proteins in a single experiment.

Jakob was intrigued to find many proteins that are not permanently damaged by reactive oxygen species but actually use amino acids known as cysteines to sense oxidative stress.

"In my lab, we have been working for a long time on proteins that use cysteine as a reactive oxygen sensor," Jakob said. "With this new technique, we discovered scores of novel proteins that are sensitive towards reactive oxygen species. Interestingly, we found that many of the proteins that we identified are important for the cells to survive oxidative stress conditions." Jakob and her team now are using this powerful technique to gain fundamental insights into the molecular mechanism of aging and the role that oxidative stress plays in this process.

"Because oxidative stress plays such a prominent role in all these diseases, we want to understand why some cells and organisms can cope with the dangers of oxidative stress, while others die," said Lars Leichert, a postdoctoral research fellow in Jakob's lab and first author of the study. Such insights might lead to the development of more powerful and effective anti-oxidant strategies.

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And because runaway neuronal death is a hallmark of Alzheimer's disease, spinal cord injury and other neurological injuries or illness, insights into mechanisms controlling neuronal survival are bound to be useful for medical research, the scientists say.

"We believe other mRNAs, and other transcription factors, may play key roles as well," Dr. Jaffrey says. "This exciting work marks a big step forward in our understanding of neurodevelopment, as well as neurological health and disease."

This work was supported by the Paralyzed Veterans of America, the U.S. National Institutes of Health, the National Alliance for Autism Research, the Klingenstein Foundation and the Charles A. Dana Foundation.

Co-researchers include Dr. Ulrich Hengst of Weill Cornell Medical College, as well as Dr. Nadya G. Gurskaya and Dr. Konstantin Lukyanov of the Russian Academy of Sciences, Moscow.

Weill Cornell Medical College

Weill Cornell Medical College, Cornell University's medical school located in New York City, is committed to excellence in research, teaching, patient care and the advancement of the art and science of medicine, locally, nationally and globally. Weill Cornell, which is a principal academic affiliate of NewYork-Presbyterian Hospital, offers an innovative curriculum that integrates the teaching of basic and clinical sciences, problem-based learning, office-based preceptorships, and primary care and doctoring courses. Physicians and scientists of Weill Cornell Medical College are engaged in cutting-edge research in areas such as stem cells, genetics and gene therapy, geriatrics, neuroscience, structural biology, cardiovascular medicine, infectious disease, obesity, cancer, psychiatry and public health -- and continue to delve ever deeper into the molecular basis of disease in an effort to unlock the mysteries of the human body in health and sickness. In its commitment to global health and education, the Medical College has a strong presence in places such as Qatar, Tanzania, Haiti, Brazil, Austria and Turkey. Through the historic Weill Cornell Medical College in Qatar, the Medical College is the first in the U.S. to offer its M.D. degree overseas. Weill Cornell is the birthplace of many medical advances -- including the development of the Pap test for cervical cancer, the synthesis of penicillin, the first successful embryo-biopsy pregnancy and birth in the U.S., the first clinical trial of gene therapy for Parkinson's disease, the first indication of bone marrow's critical role in tumor growth, and most recently, the world's first successful use of deep brain stimulation to treat a minimally-conscious brain-injured patient.

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