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NetWalker Finds Protein Damage Clues

July 8, 2011 | Melissa Marino

Molecular Biosystems

Reactive molecules generated in the body – by toxic drugs, environmental chemicals and even the body’s own natural processes – can attack and chemically modify proteins to produce protein “adducts” which may play a role in human diseases. But just how these adducts are involved in toxicity and cellular responses to oxidant damage is unclear.

To facilitate such studies, Bing Zhang, Ph.D., and colleagues have developed a systems approach called NetWalker that integrates data on protein adduction, gene expression, protein-DNA interactions and protein-protein interactions.

Their study – featured on the cover of the July Molecular Biosystems – demonstrates how this approach can predict which protein adducts may act as stress sensors and mechanisms through which they regulate gene expression. Testing this approach with the reactive molecule HNE, they identified several protein “sensors” of HNE and the signaling networks to which they belong. The findings provide novel insights into oxidant stress, which has been implicated in complex human diseases such as cancer, atherosclerosis and neurodegenerative diseases.