bims-noxint 2021-06-20 papers

Issue of 2021–06–20
two papers selected by
Laia Caja Puigsubira, Uppsala University

Free Radic Biol Med. 2021 Jun 14. pii: S0891-5849(21)00373-7. [Epub ahead of print]

Nitric Oxide and heme-NO stimulate superoxide production by NADPH Oxidase 5.

Elizabeth A Sweeny, Andrew P Hunt, Allison E Batka, Simon Schlanger, Nicolai Lehnert, Dennis J Stuehr.

Nitric oxide (NO) is a ubiquitous cell signaling molecule which mediates widespread and diverse processes in the cell. These NO dependent effects often involve activation (e.g. NO binding to the heme group of soluble guanylyl cyclase for cGMP production) or inactivation (e.g. S-nitrosation) of protein targets. We studied the effect of NO and heme-NO on the transmembrane signaling enzyme NADPH oxidase 5 (NOX5), a heme protein which produces superoxide in response to increases in intracellular calcium. We found that treatment with NO donors increases NOX5 activity through heme-dependent effects, and that this effect could be recapitulated by the addition of heme-NO. This work adds to our understanding of NOX5 regulation in the cell but also provides a framework for understanding how NO could cause widespread changes in hemeprotein activity based on different affinities for heme v. heme-NO, and helps explain the opposing roles NO plays in activation and inactivation of hemeprotein targets.

Keywords: Heme; Heme-NO; NADPH oxidase; NOX5; Nitric Oxide; Superoxide

DOI: https://doi.org/10.1016/j.freeradbiomed.2021.06.008

Front Immunol. 2021 ;12 629167

Neutrophil Extracellular Traps in Dengue Are Mainly Generated NOX-Independently.

Fadel Muhammad Garishah, Nils Rother, Silvita Fitri Riswari, Bachti Alisjahbana, Gijs J Overheul, Ronald P van Rij, André van der Ven, Johan van der Vlag, Quirijn de Mast.

Neutrophil extracellular traps (NETs) are increasingly recognized to play a role in the pathogenesis of viral infections, including dengue. NETs can be formed NADPH oxidase (NOX)-dependently or NOX-independently. NOX-independent NETs can be induced by activated platelets and are very potent in activating the endothelium. Platelet activation with thrombocytopenia and endothelial dysfunction are prominent features of dengue virus infection. We postulated that dengue infection is associated with NOX-independent NET formation, which is related to platelet activation, endothelial perturbation and increased vascular permeability. Using our specific NET assays, we investigated the time course of NET formation in a cohort of Indonesian dengue patients. We found that plasma levels of NETs were profoundly elevated and that these NETs were predominantly NOX-independent NETs. During early recovery phase (7-13 days from fever onset), total NETs correlated negatively with platelet number and positively with platelet P-selectin expression, the binding of von Willebrand factor to platelets and levels of Syndecan-1. Patients with gall bladder wall thickening, an early marker of plasma leakage, had a higher median level of total NETs. Ex vivo, platelets induced NOX-independent NET formation in a dengue virus non-structural protein 1 (NS1)-dependent manner. We conclude that NOX-independent NET formation is enhanced in dengue, which is most likely mediated by NS1 and activated platelets.

Keywords: NADPH-oxidase independent; NET formation; dengue; neutrophil extracellular traps; plasma leakage; platelets

DOI: https://doi.org/10.3389/fimmu.2021.629167