Rac/Rho pathway regulates actin depolymerization induced by aminoglycoside antibiotics

Journal of Neuroscience Research
Hongyan JiangJochen Schacht

Abstract

Stress stimuli can lead to remodeling of the actin cytoskeleton and subsequent alteration of cell adhesion and permeation as well as cell functions and cell fate. We investigated redox-dependent Rho GTPase-linked pathways controlling the actin cytoskeleton in the inner ear of the CBA mouse, by using aminoglycoside antibiotics as a noxious stimulus that causes loss of sensory cells via the formation of reactive oxygen species. Kanamycin treatment in vivo interfered with the formation of F-actin, disturbed the arrangement of beta-actin in the stereocilia of outer hair cells, and altered the intermittent adherens junction/tight junction complexes between outer hair cells and supporting cells. The drug treatment also activated Rac1 and promoted the formation of the complex of Rac1 and p67phox while decreasing the activity of RhoA and reducing the formation of the RhoA/p140mDia complex. In inner-ear-derived cell lines, expression of mutated Rac1 changed the structural arrangement of F-actin and diminished the immunoreactivity of p140mDia. These findings suggest that actin depolymerization induced by kanamycin is mediated by Rac1 activation, followed by the formation of superoxide by NADPH oxidase. These changes will ultimately contr...Continue Reading

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Citations

Feb 19, 2013·Pflügers Archiv : European journal of physiology·Takahiko NagakiHideichi Shinkawa
Jun 16, 2012·Proceedings of the National Academy of Sciences of the United States of America·Tanja MattErik C Böttger
Sep 8, 2012·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Fu-Quan ChenSu-Hua Sha
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Aug 29, 2019·Biomedical Engineering Letters·Jae-Hun LeeMin Young Lee
Sep 10, 2020·Cells·Mohaned BenzartiJohannes Meiser

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