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Published on: February 7, 2018
An "Oxidative Stress Clock" Nanoprobe Reveals the Therapeutic Time Window for Antioxidant Intervention in
Xia Zhang1, Guocheng Li1, Jiaqi Yin1
1College of Chemistry, Chemical Engineering and Materials Science, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Institute of Molecular and Nano Science, Shandong Normal University, Jinan250014, P. R. China.
Abstract:
The antioxidant treatment for atherosclerosis has presented a paradox: theoretically feasible but clinically ineffective. In this study, we developed an "oxidative stress clock" nanoprobe to dynamically monitor oxidative stress at different stages of atherosclerosis, thereby dissecting the optimal time window for antioxidant intervention. This probe could simultaneously and specifically recognize hydrogen peroxide, protein sulfenylation, and protein phosphorylation in vitro and in vivo, enabling accurate mapping of the evolution of oxidative stress during disease progression. Using this probe, we discovered that the effective window for antioxidant intervention is limited to the stage of reversible protein oxidative modification. However, clinical ultrasound imaging identifies plaques well after this critical window, which directly contributes to the clinical failure of antioxidant therapy. Furthermore, the underlying molecular mechanism driving oxidative stress-mediated atherosclerosis progression (ox-LDL→H2O2→EGFR/Src/PTP1B-SOH→p-MAPK→atherosclerosis) was uncovered.
