title: Activation of the low molecular weight protein tyrosine phosphatase in keratinocytes exposed to hyperosmotic stress.
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.
authors.affiliation: Departamento de Bioquímica, Instituto de Biologia, Universidade Estadual de Campinas, Campinas, São Paulo, Brazil.
authors.forename: Rodrigo A
authors.initials: RA
authors.lastname: Silva
authors.affiliation: Departamento de Bioquímica (Campus São Paulo), Universidade Federal de São Paulo, São Paulo, São Paulo, Brazil.
authors.forename: Marcelly V
authors.initials: MV
authors.lastname: Palladino
authors.affiliation: Departamento de Bioquímica (Campus São Paulo), Universidade Federal de São Paulo, São Paulo, São Paulo, Brazil.
authors.forename: Renan P
authors.initials: RP
authors.lastname: Cavalheiro
authors.affiliation: Departamento de Bioquímica, Instituto de Biologia, Universidade Estadual de Campinas, Campinas, São Paulo, Brazil.
authors.forename: Daisy
authors.initials: D
authors.lastname: Machado
authors.affiliation: Departamento de Bioquímica, Instituto de Biologia, Universidade Estadual de Campinas, Campinas, São Paulo, Brazil.
authors.forename: Bread L G
authors.initials: BL
authors.lastname: Cruz
authors.affiliation: Departamento de Bioquímica (Campus São Paulo), Universidade Federal de São Paulo, São Paulo, São Paulo, Brazil.
authors.forename: Edgar J
authors.initials: EJ
authors.lastname: Paredes-Gamero
authors.affiliation: Departamento de Bioquímica, Instituto de Biologia, Universidade Estadual de Campinas, Campinas, São Paulo, Brazil.
authors.forename: Maria C C
authors.initials: MC
authors.lastname: Gomes-Marcondes
authors.affiliation: Departamento de Química e Bioquímica, IBB, Universidade Estadual Paulista, Botucatu, São Paulo, Brazil.
authors.forename: Willian F
authors.initials: WF
authors.lastname: Zambuzzi
authors.affiliation: Departamento de Genética e Biologia Evolutiva, Universidade de São Paulo, São Paulo, São Paulo, Brazil.
authors.forename: Luciana
authors.initials: L
authors.lastname: Vasques
authors.affiliation: Departamento de Bioquímica (Campus São Paulo), Universidade Federal de São Paulo, São Paulo, São Paulo, Brazil.
authors.forename: Helena B
authors.initials: HB
authors.lastname: Nader
authors.affiliation: Centro de Ciências Naturais e Humanas, Universidade Federal do ABC, Santo André, São Paulo, Brazil.
authors.forename: Ana Carolina S
authors.initials: AC
authors.lastname: Souza
authors.affiliation: Departamento de Bioquímica, Instituto de Biologia, Universidade Estadual de Campinas, Campinas, São Paulo, Brazil; Departamento de Bioquímica (Campus São Paulo) and Departamento de Ciências Biológicas (Campus Diadema), Universidade Federal de São Paulo, São Paulo, São Paulo, Brazil.
authors.forename: Giselle Z
authors.initials: GZ
authors.lastname: Justo
mesh_terms: D051339:Actin Depolymerizing Factors / Q000378:metabolism; D002460:Cell Line; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000235:genetics / Q000378:metabolism; D005980:Glutathione Reductase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism*; D009997:Osmotic Pressure; D010766:Phosphorylation; D017027:Protein Tyrosine Phosphatases / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D050799:STAT5 Transcription Factor / Q000378:metabolism; D019061:src-Family Kinases / Q000378:metabolism
chemical_list: D051339:Actin Depolymerizing Factors; D011518:Proto-Oncogene Proteins; D050799:STAT5 Transcription Factor; D005979:Glutathione Peroxidase; D005980:Glutathione Reductase; D019061:src-Family Kinases; C490429:ACP1 protein, human; D017027:Protein Tyrosine Phosphatases; D005978:Glutathione