Scientists at Sanford Research have just developed a new model that could have lasting implications for some of the world’s most dangerous diseases like cancer, diabetes, neurodegeneration, heart disease, and respiratory distress syndrome.
The new study, led by Peter Vitiello, PhD, Associate Scientist, Children's Health Research Center at Sanford Research, was recently published in Free Radical Biology and Medicine, a journal of the Society for Redox Biology and Medicine (SfRBM).
Many tissue processes and disease pathologies in the human body are influenced by disturbances in cellular redox, an imbalance in the generation and detoxification of chemical oxidants. Thioredoxin-1 (Trx1) is an antioxidant enzyme synthesized by every human cell to detoxify proteins damaged by chemical oxidants. Understanding fundamental molecular functions of Trx1 may provide new therapeutic strategies to prevent disease progression during cellular redox imbalance.
To understand how Trx1 functions during redox alterations and disease pathogenesis, the study described a novel mouse genetically engineered to identify proteins detoxified by Trx1 in lung.
“As we better understand how molecules sense and regulate cellular responses to redox imbalances at the core of so many human disease, we can then improve therapies and treatments that will save lives,” said Dr. Peter Vitiello an Associate Scientist at Sanford Research and SFRBM member. “By creating this transgenic mouse designed to identify proteins targeted by thioredoxin-1, we can learn new information about molecular responses in cells during redox perturbations which we hope will lead to new therapeutic approaches that hinder progression of diseases such as respiratory distress syndrome and neurodegeneration.”
Specifically, Dr. Vitiello’s research team engineered a mutation in the thioredoxin-1 mouse gene that stabilizes interactions with proteins targeted for detoxification by thioredoxin-1. The mutant thioredoxin-1 is then purified along with any bound proteins which are subsequently identified by mass spectrometry. To demonstrate how this technology can be applied to understand disease processes, transgenic mice were treated with excess oxygen to cause lung injury, and Dr. Vitiello found that there were unique sets proteins bound to thioredoxin-1 which were exclusively detected in either control of treatment groups.