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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

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

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Autor(es):
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Silva, Rodrigo A. [1] ; Palladino, Marcelly V. [2] ; Cavalheiro, Renan P. [2] ; Machado, Daisy [1] ; Cruz, Bread L. G. [1] ; Paredes-Gamero, Edgar J. [2] ; Gomes-Marcondes, Maria C. C. [1] ; Zambuzzi, Willian F. [3] ; Vasques, Luciana [4] ; Nader, Helena B. [2] ; Souza, Ana Carolina S. [5] ; Justo, Giselle Z. [2, 6, 1]
Número total de Autores: 12
Afiliação do(s) autor(es):
[1] Univ Estadual Campinas, Dept Bioquim, Inst Biol, Sao Paulo - Brazil
[2] Univ Fed Sao Paulo, Dept Bioquim, Sao Paulo, SP - Brazil
[3] Univ Estadual Paulista, Dept Quim & Bioquim, IBB, Sao Paulo - Brazil
[4] Univ Sao Paulo, Dept Genet & Biol Evolut, Sao Paulo, SP - Brazil
[5] Univ Fed ABC, Ctr Ciencias Nat & Humanas, Sao Paulo - Brazil
[6] Univ Fed Sao Paulo, Dept Ciencias Biol, Sao Paulo, SP - Brazil
Número total de Afiliações: 6
Tipo de documento: Artigo Científico
Fonte: PLoS One; v. 10, n. 3 MAR 17 2015.
Citações Web of Science: 1
Resumo

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. (AU)

Processo FAPESP: 06/07315-3 - Efeitos da riboflavina sobre as vias de sobrevivência e morte de queratinócitos: implicações na terapêutica dermatológica
Beneficiário:Rodrigo Augusto da Silva
Modalidade de apoio: Bolsas no Brasil - Doutorado Direto