1.
Empagliflozin reduces oxidative stress through inhibition of the novel inflammation/NHE/[Na+]c/ROS-pathway in human endothelial cells.
Uthman, L, Li, X, Baartscheer, A, Schumacher, CA, Baumgart, P, Hermanides, J, Preckel, B, Hollmann, MW, Coronel, R, Zuurbier, CJ, et al
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. 2022;:112515
Abstract
Inflammation causing oxidative stress in endothelial cells contributes to heart failure development. Sodium/glucose cotransporter 2 inhibitors (SGLT2i's) were shown to reduce heart failure hospitalization and oxidative stress. However, how inflammation causes oxidative stress in endothelial cells, and how SGLT2i's can reduce this is unknown. Here we hypothesized that 1) TNF-α activates the Na+/H+ exchanger (NHE) and raises cytoplasmatic Na+ ([Na+]c), 2) increased [Na+]c causes reactive oxygen species (ROS) production, and 3) empagliflozin (EMPA) reduces inflammation-induced ROS through NHE inhibition and lowering of [Na+]c in human endothelial cells. Human umbilical vein endothelial cells (HUVECs) and human coronary artery endothelial cells (HCAECs) were incubated with vehicle (V), 10 ng/ml TNF-α, 1 µM EMPA or the NHE inhibitor Cariporide (CARI, 10 µM) and NHE activity, intracellular [Na+]c and ROS were analyzed. TNF-α enhanced NHE activity in HCAECs and HUVECs by 92% (p < 0.01) and 51% (p < 0.05), respectively, and increased [Na+]c from 8.2 ± 1.6 to 11.2 ± 0.1 mM (p < 0.05) in HCAECs. Increasing [Na+]c by ouabain elevated ROS generation in both HCAECs and HUVECs. EMPA inhibited NHE activity in HCAECs and in HUVECs. EMPA concomitantly lowered [Na+]c in both cell types. In both cell types, TNF α-induced ROS was lowered by EMPA or CARI, with no further ROS lowering by EMPA in the presence of CARI, indicating EMPA attenuated ROS through NHE inhibition. In conclusion, inflammation induces oxidative stress in human endothelial cells through NHE activation causing elevations in [Na+]c, a process that is inhibited by EMPA through NHE inhibition.
2.
Synthesis, crystal structure and hydrolysis activity of a novel heterobinuclear cobalt(ІІІ) sodium(І) Schiff base complex.
Li, X, Liu, Z, Xu, Y, Wang, D
Journal of inorganic biochemistry. 2017;:37-44
Abstract
A novel heterobinuclear complex [CoNa(C15H10NO4F)2(CH3OH)]2 with Schiff base (C15H10NO4F: 2-amino-4-fluorobenzoic acid-3-methoxysalicylaldehyde) was synthesized and characterized by IR and 1H NMR spectroscopy, elemental analysis and single crystal X-ray diffraction. X-ray crystallography reveals that the cobalt atom is six-coordinated by two nitrogen atoms from -CN-, two carboxylate oxygen atoms and two hydroxyl oxygen atoms in different ligands, while the sodium atom is seven-coordinated by two methoxy oxygen atoms, two hydroxyl oxygen atoms in different ligands, two oxygen atoms in the same carboxylate and one oxygen atom of solvent methanol. The reaction results of the complex with the p-nitrophenylphosphate (pNPP) and the adenosine monophosphate (AMP) reveal that the complex can hydrolyze phosphoester bonds. Then the DNA-hydrolysis activity is studied experimentally and theoretically, indicating that the complex can effectively hydrolyze the pBR322 supercoiled plasmid DNA. The molecular docking technology predicts the best binding site and binding affinity between the complex and DNA, and then the catalytic mechanism of hydrolysis is supposed. The study results suggest that the Schiff base metal complex, as a potent artificial enzyme, may find its applications in catalytic hydrolysis and biotechnological areas.