1. Molecular Mechanism of NL13 Peptide of Adenosyl Homocysteinase Against ER Stress through Nrf2 Signaling Cascade.
- Author
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Sarkar, Purabi, Amin, Karan Naresh, Balakrishnan, Ranjith, Ramkumar, Kunka Mohanram, and Arockiaraj, Jesu
- Abstract
Purpose: This study investigates the regulatory role of NL13, a compound derived from adenosyl homocysteinase of cyanobacteria, on ER stress-induced apoptosis in endothelial cells by modulating the Keap1-Nrf2 signaling pathway. Methods: Human endothelial cells (EA.hy926) were exposed to thapsigargin (TPG) to induce ER stress and then pretreated with varying concentrations of NL13. The study employed qPCR to assess changes in gene expression related to ER stress markers (GRP78, CHOP, ATF6, and PERK) and Nrf2. Additionally, reactive oxygen species (ROS) levels and the expression of apoptotic proteins (Bcl2 and Bax) were evaluated. In-silico molecular docking was used to explore potential interactions between NL13 and Keap1-Nrf2. Results: NL13 significantly reduced oxidative and ER stress in endothelial cells. It downregulated ER stress markers (GRP78, CHOP, ATF6, PERK) while upregulating Nrf2 expression. NL13 also decreased ROS formation and modulated the expression of apoptotic proteins, increasing Bcl2 and decreasing Bax. Molecular docking revealed interactions of NL13 with critical amino acids in Keap1-Nrf2, suggesting a functional binding that enhances Nrf2 signaling. Conclusion: NL13 exerts cytoprotective effects against ER stress in endothelial cells by modulating the Keap1-Nrf2 signaling pathway and reducing apoptosis. These findings highlight the potential of NL13 as a therapeutic agent for conditions involving ER stress and oxidative damage. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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