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Evaluation of Bioenergetic Function in Cerebral Vascular Endothelial Cells
Published on: November 19, 2016
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Neurogranin expression regulates mitochondrial function and redox balance in endothelial cells
Ashton N Jorgensen1, Nabil A Rashdan2, K N Shashanka Rao3
1Department of Pharmacology, Toxicology, and Neuroscience, Louisiana State University Health Sciences Center, Shreveport, LA, 71103, USA.
Redox Biology
|February 15, 2024
Summary
Neurogranin (Ng) deficiency in endothelial cells impairs mitochondrial function and increases oxidative stress, contributing to vascular dysfunction. MitoEbselen treatment rescues these effects, highlighting Ng
Area of Science:
- Cardiovascular Biology
- Mitochondrial Medicine
- Neurobiology
Background:
- Endothelial dysfunction is an early indicator of vascular diseases, often linked to mitochondrial issues.
- Neurogranin (Ng), known for its role in neuronal calcium signaling, is now found in endothelial cells.
Purpose of the Study:
- To investigate the role of endothelial Neurogranin (Ng) in regulating mitochondrial function and oxidative stress in vascular health.
- To determine the impact of Ng deficiency on endothelial activation and cardiovascular disease progression.
Main Methods:
- Utilized endothelial-specific Ng knockout mice (Cre-CDH5-Ngf/f) and human aortic endothelial cells (HAECs).
- Employed label-free quantification proteomics, western blotting, immunofluorescence staining, Seahorse assay, and RoGFP-Orp1 for ROS detection.
- Investigated the therapeutic potential of MitoEbselen.
Main Results:
- Ng depletion in HAECs led to increased Ca2+-CaM signaling, endothelial activation, and redox imbalance.
- Ng knockout mice showed impaired flow-mediated dilation (FMD).
- Ng deficiency resulted in mitochondrial dysfunction, decreased mitochondrial respiration, and elevated mitochondrial ROS (mtROS) production.
- MitoEbselen treatment restored mitochondrial respiration, reduced mtROS, and improved eNOS expression and nitric oxide (NO) levels.
Conclusions:
- Endothelial Ng plays a crucial role in maintaining mitochondrial function and redox balance.
- Ng deficiency exacerbates endothelial dysfunction through increased mtROS and impaired NO bioavailability.
- Targeting mitochondrial ROS with agents like MitoEbselen may offer therapeutic benefits for vascular diseases associated with Ng dysfunction.
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