Activation of the Low Molecular Weight Protein Tyrosine Phosphatase in Keratinocytes Exposed to Hyperosmotic Stress

Activation of the Low Molecular Weight Protein Tyrosine Phosphatase in Keratinocytes Exposed to Hyperosmotic Stress

Author Silva, Rodrigo A. Google Scholar
Palladino, Marcelly V. Autor UNIFESP Google Scholar
Cavalheiro, Renan Pelluzzi Autor UNIFESP Google Scholar
Machado, Daisy Google Scholar
Cruz, Bread L. G. Google Scholar
Paredes-Gamero, Edgar Julian Autor UNIFESP Google Scholar
Gomes-Marcondes, Maria C. C. Google Scholar
Zambuzzi, Willian F. Google Scholar
Vasques, Luciana Google Scholar
Nader, Helena Bonciani Autor UNIFESP Google Scholar
Souza, Ana Carolina S. Google Scholar
Justo, Giselle Zenker Autor UNIFESP Google Scholar
Institution Universidade Estadual de Campinas (UNICAMP)
Universidade Federal de São Paulo (UNIFESP)
Univ Estadual Paulista
Universidade de São Paulo (USP)
Universidade Federal do ABC (UFABC)
Abstract Herein, we provide new contribution to the mechanisms involved in keratinocytes response to hyperosmotic shock showing, for the first time, the participation of Low Molecular Weight Protein Tyrosine Phosphatase (LMWPTP) activity in this event. We reported that sorbitol-induced osmotic stress mediates alterations in the phosphorylation of pivotal cytoskeletal proteins, particularly Src and cofilin. Furthermore, an increase in the expression of the phosphorylated form of LMWPTP, which was followed by an augment in its catalytic activity, was observed. of particular importance, these responses occurred in an intracellular milieu characterized by elevated levels of reduced glutathione (GSH) and increased expression of the antioxidant enzymes glutathione peroxidase and glutathione reductase. Altogether, our results suggest that hyperosmostic stress provides a favorable cellular environment to the activation of LMWPTP, which is associated with increased expression of antioxidant enzymes, high levels of GSH and inhibition of Src kinase. Finally, the real contribution of LMWPTP in the hyperosmotic stress response of keratinocytes was demonstrated through analysis of the effects of ACP1 gene knockdown in stressed and non-stressed cells. LMWPTP knockdown attenuates the effects of sorbitol induced-stress in HaCaT cells, mainly in the status of Src kinase, Rac and STAT5 phosphorylation and activity. These results describe for the first time the participation of LMWPTP in the dynamics of cytoskeleton rearrangement during exposure of human keratinocytes to hyperosmotic shock, which may contribute to cell death.
Language English
Sponsor Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Grant number FAPESP: 2006/07315-3
CNPq: PQ-2
Date 2015-03-17
Published in Plos One. San Francisco: Public Library Science, v. 10, n. 3, 19 p., 2015.
ISSN 1932-6203 (Sherpa/Romeo, impact factor)
Publisher Public Library Science
Extent 19
Origin http://dx.doi.org/10.1371/journal.pone.0119020
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000351284600044
URI http://repositorio.unifesp.br/handle/11600/38892

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