Article Summary:
Exploring the Metabolism of NAD+ and NMN in Vascular Endothelial Cells
Introduction:
- Nicotinamide adenine dinucleotide (NAD+) is vital for cellular processes and signaling.
- Proper NAD+ metabolism is crucial for cellular energy turnover.
- Abnormal NAD+ and NMN metabolism can cause cell aging and cardiovascular diseases.
- Metabolism of NAD+ and NMN in vascular endothelium differs between species and locations.
- Understanding these differences is important for modulating the NAD+ system and comparing research results.
Key Cellular Processes and Signaling:
- NAD+ is involved in redox reactions and serves as a substrate in signaling processes.
- Enzymes like sirtuins and PARPs are responsible for NAD+ catabolism.
- NAD+-dependent signaling pathways impact cell cycle progression, transcriptional regulation, and DNA repair.
- Imbalances in NAD+ synthesis and degradation can lead to pathologies.
Extracellular NAD+ and NMN Metabolism:
- Precursor recycling is the main approach to regulate NAD+ levels.
- Extracellular enzymes like CD38 and CD73 are important for NAD+ and NMN cleavage.
- Endothelial cells play a role in secretion, chemical transport, and blood regulation.
- Dysfunctional endothelium is linked to various vascular diseases.
- Targeting ectonucleotidases as therapeutic strategies can treat vascular diseases.
Materials and Methods:
- Various reagents and cell culture mediums were used for the study.
- Ethical guidelines and approvals were followed for experiments on mice.
- Different endothelial cell types were tested, and NAD+ and NMN-degrading activities were determined using HPLC.
- Immunofluorescence analysis and specific inhibitors were used to identify the enzymes involved.
- Statistical analysis was conducted using t-tests and ANOVA.
Metabolism of NAD+ and NMN in Endothelial Cells:
- Endothelial cells exhibit different NAD+ and NMN metabolism, indicating enzyme-substrate affinities.
- CD73 and CD38 are the main enzymes responsible for NAD+ and NMN hydrolysis.
- CD73 knockout reduces NMN consumption, implicating its involvement in NMN metabolism.
- Differences in enzyme affinity for NAD+ and NMN substrates were observed.
Implications and Limitations:
- NAD+ and NMN impact various functions like inflammation and calcium signaling.
- Enhancement therapies for NAD+ show systemic benefits.
- CD38 and CD73 play roles in calcium regulation, inflammation, and vasoprotection.
- Measurements and cultural conditions affect NAD+ and NMN metabolism in endothelial cells.
- Standardization and consistent research are crucial in this area.
Conclusion:
- The study examined NAD+ and NMN metabolism in different vascular endothelial cells.
- CD38 and CD73 were identified as the main enzymes involved in their hydrolysis.
- Differences in NAD+ and NMN metabolism highlight the need for standardized research.
- Extracellular NAD+ and NMN metabolism influences various cellular functions and diseases.
Title of paper: Differences in Extracellular NAD(+) and NMN Metabolism on the Surface of Vascular Endothelial Cells
Author(s): Jablonska P, Mierzejewska P, Tomczyk M, Koszalka P, Franczak M, Kawecka A, Kutryb-Zajac B, Braczko A, Smolenski RT, Slominska EM.
Year published: 2022
Published in: Biology (Basel)
Original article can be found here.
