Simultaneous fluorescence imaging of Golgi O2•- and Golgi H2O2 in mice with hypertension

Abstract

Hypertensive cardiovascular disease is a persistent threat to public health. Elucidating the pathogenesis of hypertension is expected to provide more highly targeted therapies for patients. To date, reactive oxygen species (ROS) induced endothelial nitric oxide synthase (eNOS) uncoupling are generally considered to be common phenomena in hypertension. However, the critical factor contribute to persistent eNOS uncoupling remains poorly understood. Herein, we established a fluorescence probe, Gol_ROS, for the multicolored and simultaneous detection of Golgi O₂^•- and H₂O₂ in situ. We successfully detected increases in Golgi ROS levels in hypertensive mice and evaluated the pharmaceutical effects of various antihypertensive drugs. More importantly, we identified the ROS post-transcriptional modification sites on dihydrofolate reductase (DHFR). Altogether, we propose a novel therapeutic target for hypertension, which will promote the development of new antihypertensive drugs, and also developed an ideal fluorescence probe to study in situ Golgi O₂^•- and H₂O₂ changes in various biochemical processes.

Keywords: Fluorescence imaging; Golgi oxidative stress; Hydrogen peroxide; Hypertension; Superoxide anion radical.