Activation of the Low Molecular Weight Protein Tyrosine Phosphatase in Keratinocytes Exposed to Hyperosmotic Stress
Autor(a) principal: | |
---|---|
Data de Publicação: | 2015 |
Outros Autores: | , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNIFESP |
Texto Completo: | http://repositorio.unifesp.br/handle/11600/38892 http://dx.doi.org/10.1371/journal.pone.0119020 |
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. |
id |
UFSP_bdc4984234cef4b39163ec22f3571665 |
---|---|
oai_identifier_str |
oai:repositorio.unifesp.br:11600/38892 |
network_acronym_str |
UFSP |
network_name_str |
Repositório Institucional da UNIFESP |
repository_id_str |
3465 |
spelling |
Silva, Rodrigo A.Palladino, Marcelly V. [UNIFESP]Cavalheiro, Renan Pelluzzi [UNIFESP]Machado, DaisyCruz, Bread L. G.Paredes-Gamero, Edgar Julian [UNIFESP]Gomes-Marcondes, Maria C. C.Zambuzzi, Willian F.Vasques, LucianaNader, Helena Bonciani [UNIFESP]Souza, Ana Carolina S.Justo, Giselle Zenker [UNIFESP]Universidade Estadual de Campinas (UNICAMP)Universidade Federal de São Paulo (UNIFESP)Univ Estadual PaulistaUniversidade de São Paulo (USP)Universidade Federal do ABC (UFABC)2016-01-24T14:40:15Z2016-01-24T14:40:15Z2015-03-17Plos One. San Francisco: Public Library Science, v. 10, n. 3, 19 p., 2015.1932-6203http://repositorio.unifesp.br/handle/11600/38892http://dx.doi.org/10.1371/journal.pone.0119020WOS000351284600044.pdf10.1371/journal.pone.0119020WOS:000351284600044Herein, 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.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)Univ Estadual Campinas, Dept Bioquim, Inst Biol, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Bioquim, São Paulo, SP, BrazilUniv Estadual Paulista, Dept Quim & Bioquim, IBB, São Paulo, BrazilUniv São Paulo, Dept Genet & Biol Evolut, São Paulo, SP, BrazilUniv Fed ABC, Ctr Ciencias Nat & Humanas, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Ciencias Biol, São Paulo, SP, BrazilUniversidade Federal de São Paulo, Dept Bioquim, São Paulo, SP, BrazilUniversidade Federal de São Paulo, Dept Ciencias Biol, São Paulo, SP, BrazilFAPESP: 2006/07315-3CNPq: PQ-2Web of Science19engPublic Library SciencePlos OneActivation of the Low Molecular Weight Protein Tyrosine Phosphatase in Keratinocytes Exposed to Hyperosmotic Stressinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UNIFESPinstname:Universidade Federal de São Paulo (UNIFESP)instacron:UNIFESPORIGINALWOS000351284600044.pdfapplication/pdf1597858${dspace.ui.url}/bitstream/11600/38892/1/WOS000351284600044.pdf3f3d4bbbeee9225b871d111d44067d2aMD51open accessTEXTWOS000351284600044.pdf.txtWOS000351284600044.pdf.txtExtracted texttext/plain67547${dspace.ui.url}/bitstream/11600/38892/9/WOS000351284600044.pdf.txtdbba48dfcb8d77d588a95428a033edc5MD59open accessTHUMBNAILWOS000351284600044.pdf.jpgWOS000351284600044.pdf.jpgIM Thumbnailimage/jpeg7695${dspace.ui.url}/bitstream/11600/38892/11/WOS000351284600044.pdf.jpgc97cb980a765e8e2beb558b3539f46b4MD511open access11600/388922023-06-05 19:24:11.537open accessoai:repositorio.unifesp.br:11600/38892Repositório InstitucionalPUBhttp://www.repositorio.unifesp.br/oai/requestopendoar:34652023-06-05T22:24:11Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)false |
dc.title.en.fl_str_mv |
Activation of the Low Molecular Weight Protein Tyrosine Phosphatase in Keratinocytes Exposed to Hyperosmotic Stress |
title |
Activation of the Low Molecular Weight Protein Tyrosine Phosphatase in Keratinocytes Exposed to Hyperosmotic Stress |
spellingShingle |
Activation of the Low Molecular Weight Protein Tyrosine Phosphatase in Keratinocytes Exposed to Hyperosmotic Stress Silva, Rodrigo A. |
title_short |
Activation of the Low Molecular Weight Protein Tyrosine Phosphatase in Keratinocytes Exposed to Hyperosmotic Stress |
title_full |
Activation of the Low Molecular Weight Protein Tyrosine Phosphatase in Keratinocytes Exposed to Hyperosmotic Stress |
title_fullStr |
Activation of the Low Molecular Weight Protein Tyrosine Phosphatase in Keratinocytes Exposed to Hyperosmotic Stress |
title_full_unstemmed |
Activation of the Low Molecular Weight Protein Tyrosine Phosphatase in Keratinocytes Exposed to Hyperosmotic Stress |
title_sort |
Activation of the Low Molecular Weight Protein Tyrosine Phosphatase in Keratinocytes Exposed to Hyperosmotic Stress |
author |
Silva, Rodrigo A. |
author_facet |
Silva, Rodrigo A. Palladino, Marcelly V. [UNIFESP] Cavalheiro, Renan Pelluzzi [UNIFESP] Machado, Daisy Cruz, Bread L. G. Paredes-Gamero, Edgar Julian [UNIFESP] Gomes-Marcondes, Maria C. C. Zambuzzi, Willian F. Vasques, Luciana Nader, Helena Bonciani [UNIFESP] Souza, Ana Carolina S. Justo, Giselle Zenker [UNIFESP] |
author_role |
author |
author2 |
Palladino, Marcelly V. [UNIFESP] Cavalheiro, Renan Pelluzzi [UNIFESP] Machado, Daisy Cruz, Bread L. G. Paredes-Gamero, Edgar Julian [UNIFESP] Gomes-Marcondes, Maria C. C. Zambuzzi, Willian F. Vasques, Luciana Nader, Helena Bonciani [UNIFESP] Souza, Ana Carolina S. Justo, Giselle Zenker [UNIFESP] |
author2_role |
author author author author author author author author author author author |
dc.contributor.institution.none.fl_str_mv |
Universidade Estadual de Campinas (UNICAMP) Universidade Federal de São Paulo (UNIFESP) Univ Estadual Paulista Universidade de São Paulo (USP) Universidade Federal do ABC (UFABC) |
dc.contributor.author.fl_str_mv |
Silva, Rodrigo A. Palladino, Marcelly V. [UNIFESP] Cavalheiro, Renan Pelluzzi [UNIFESP] Machado, Daisy Cruz, Bread L. G. Paredes-Gamero, Edgar Julian [UNIFESP] Gomes-Marcondes, Maria C. C. Zambuzzi, Willian F. Vasques, Luciana Nader, Helena Bonciani [UNIFESP] Souza, Ana Carolina S. Justo, Giselle Zenker [UNIFESP] |
description |
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. |
publishDate |
2015 |
dc.date.issued.fl_str_mv |
2015-03-17 |
dc.date.accessioned.fl_str_mv |
2016-01-24T14:40:15Z |
dc.date.available.fl_str_mv |
2016-01-24T14:40:15Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.citation.fl_str_mv |
Plos One. San Francisco: Public Library Science, v. 10, n. 3, 19 p., 2015. |
dc.identifier.uri.fl_str_mv |
http://repositorio.unifesp.br/handle/11600/38892 http://dx.doi.org/10.1371/journal.pone.0119020 |
dc.identifier.issn.none.fl_str_mv |
1932-6203 |
dc.identifier.file.none.fl_str_mv |
WOS000351284600044.pdf |
dc.identifier.doi.none.fl_str_mv |
10.1371/journal.pone.0119020 |
dc.identifier.wos.none.fl_str_mv |
WOS:000351284600044 |
identifier_str_mv |
Plos One. San Francisco: Public Library Science, v. 10, n. 3, 19 p., 2015. 1932-6203 WOS000351284600044.pdf 10.1371/journal.pone.0119020 WOS:000351284600044 |
url |
http://repositorio.unifesp.br/handle/11600/38892 http://dx.doi.org/10.1371/journal.pone.0119020 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.ispartof.none.fl_str_mv |
Plos One |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
19 |
dc.publisher.none.fl_str_mv |
Public Library Science |
publisher.none.fl_str_mv |
Public Library Science |
dc.source.none.fl_str_mv |
reponame:Repositório Institucional da UNIFESP instname:Universidade Federal de São Paulo (UNIFESP) instacron:UNIFESP |
instname_str |
Universidade Federal de São Paulo (UNIFESP) |
instacron_str |
UNIFESP |
institution |
UNIFESP |
reponame_str |
Repositório Institucional da UNIFESP |
collection |
Repositório Institucional da UNIFESP |
bitstream.url.fl_str_mv |
${dspace.ui.url}/bitstream/11600/38892/1/WOS000351284600044.pdf ${dspace.ui.url}/bitstream/11600/38892/9/WOS000351284600044.pdf.txt ${dspace.ui.url}/bitstream/11600/38892/11/WOS000351284600044.pdf.jpg |
bitstream.checksum.fl_str_mv |
3f3d4bbbeee9225b871d111d44067d2a dbba48dfcb8d77d588a95428a033edc5 c97cb980a765e8e2beb558b3539f46b4 |
bitstream.checksumAlgorithm.fl_str_mv |
MD5 MD5 MD5 |
repository.name.fl_str_mv |
Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP) |
repository.mail.fl_str_mv |
|
_version_ |
1802764183520935936 |