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Título

L-Plastin S-glutathionylation promotes reduced binding to β-actin and affects neutrophil functions

AutorDubey, Megha; Sánchez-Gómez, Francisco J. ; Lamas Peláez, Santiago ; Diskshit, Madhu
Palabras clavePosttranslational modifications
Nitric oxide
Oxidativestress
Chemotaxis
Polarization
Phagocytosis
Bactericidal activity
Diabetes
Fecha de publicación14-abr-2015
EditorElsevier
CitaciónFree Radical Biology and Medicine 86: 1- 15 (2015)
Resumen© 2015 Elsevier Inc. All rights reserved. Posttranslational modifications (PTMs) of cytoskeleton proteins due to oxidative stress associated with several pathological conditions often lead to alterations in cell function. The current study evaluates the effect of nitric oxide (DETA-NO)-induced oxidative stress-related S-glutathionylation of cytoskeleton proteins in human PMNs. By using in vitro and genetic approaches, we showed that S-glutathionylation of L-plastin (LPL) and β-actin promotes reduced chemotaxis, polarization, bactericidal activity, and phagocytosis. We identified Cys-206, Cys-283, and Cys-460 as S-thiolated residues in the β-actin-binding domain of LPL, where cys-460 had the maximum score. Site-directed mutagenesis of LPL Cys-460 further confirmed the role in the redox regulation of LPL. S-Thiolation diminished binding as well as the bundling activity of LPL. The presence of S-thiolated LPL was detected in neutrophils from both diabetic patients and db/db mice with impaired PMN functions. Thus, enhanced nitroxidative stress may results in LPL S-glutathionylation leading to impaired chemotaxis, polarization, and bactericidal activity of human PMNs, providing a mechanistic basis for their impaired functions in diabetes mellitus.
URIhttp://hdl.handle.net/10261/139901
DOI10.1016/j.freeradbiomed.2015.04.008
Identificadoresdoi: 10.1016/j.freeradbiomed.2015.04.008
issn: 1873-4596
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