Activation of the low molecular weight protein tyrosine phosphatase in keratinocytes exposed to hyperosmotic stress

• Published in: PloS one 2015-03, Vol.10 (3), p.e0119020-e0119020
• Main Authors: Silva, Rodrigo A, Palladino, Marcelly V, Cavalheiro, Renan P, Machado, Daisy, Cruz, Bread L G, Paredes-Gamero, Edgar J, Gomes-Marcondes, Maria C C, Zambuzzi, Willian F, Vasques, Luciana, Nader, Helena B, Souza, Ana Carolina S, Justo, Giselle Z
• Format: Article
• Language: English
• Subjects: Actin Depolymerizing Factors - metabolism; Activation; Antioxidants; Apoptosis; Catalysis; Catalytic activity; Cell cycle; Cell death; Cell Line; Cofilin; Cytoskeleton; Enzymes; Glutathione; Glutathione - metabolism; Glutathione peroxidase; Glutathione Peroxidase - genetics; Glutathione Peroxidase - metabolism; Glutathione reductase; Glutathione Reductase - genetics; Glutathione Reductase - metabolism; Humans; Immunoglobulins; Keratinocytes; Keratinocytes - metabolism; Low molecular weights; Mammals; Molecular weight; Osmotic Pressure; Osmotic stress; Peroxidase; Phenols (Class of compounds); Phosphatase; Phosphatases; Phosphorylation; Protein Tyrosine Phosphatases - genetics; Protein Tyrosine Phosphatases - metabolism; Protein-tyrosine-phosphatase; Proteins; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins - metabolism; Regulation; Signal transduction; Sorbitol; Src protein; src-Family Kinases - metabolism; Stat5 protein; STAT5 Transcription Factor - metabolism; Stress; Stresses; Tyrosine
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0119020

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.