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Simultaneous fluorescence imaging of Golgi O2•- and Golgi H2O2 in mice with hypertension
Hui Wang1, Cuifang Liu1, Xiaoting Zhang1
1College of Chemistry, Chemical Engineering and Materials Science, Key Laboratory of Molecular and Nano Probes, Minis-try of Education, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Institutes of Biomedical Sciences, Shandong Normal University, Jinan, 250014, People's Republic of China.
Insights
Researchers identified a new therapeutic target for hypertension by discovering reactive oxygen species (ROS) modification sites on dihydrofolate reductase (DHFR). This finding advances understanding of hypertension pathogenesis and drug development.
Area of Science:
- Biochemistry
- Cardiovascular Science
- Pharmacology
Background:
- Hypertensive cardiovascular disease poses a significant public health challenge.
- Endothelial nitric oxide synthase (eNOS) uncoupling due to reactive oxygen species (ROS) is implicated in hypertension, but the underlying causes of persistent eNOS uncoupling are unclear.
Purpose of the Study:
- To develop a novel fluorescence probe for simultaneous in situ detection of Golgi O2•− and H2O2.
- To investigate the role of Golgi ROS in hypertension pathogenesis.
- To identify novel therapeutic targets for hypertension.
Main Methods:
- Development of a novel fluorescence probe, GolROS, for detecting Golgi O2•− and H2O2.
- In situ detection of Golgi ROS in hypertensive mouse models.
- Evaluation of antihypertensive drug efficacy.
- Identification of ROS post-transcriptional modification sites on dihydrofolate reductase (DHFR).
Main Results:
- GolROS probe successfully detected increased Golgi ROS levels in hypertensive mice.
- Pharmaceutical effects of various antihypertensive drugs were evaluated.
- Specific ROS post-transcriptional modification sites on DHFR were identified.
Conclusions:
- The study proposes DHFR as a novel therapeutic target for hypertension.
- The developed GolROS probe is an effective tool for studying Golgi ROS dynamics in various biochemical processes.
- Findings contribute to the development of new antihypertensive therapies.
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, GolROS, 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.
