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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Accumulation of the SET protein in HEK293T cells and mild oxidative stress: cell survival or death signaling

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Author(s):
Leopoldino, Andreia M. [1] ; Squarize, Cristiane H. [2] ; Garcia, Cristiana B. [1] ; Almeida, Luciana O. [1] ; Pestana, Cezar R. [3] ; Polizello, Ana C. M. [3] ; Uyemura, Sergio A. [1] ; Tajara, Eloiza H. [4] ; Gutkind, J. Silvio [5] ; Curti, Carlos [3]
Total Authors: 10
Affiliation:
[1] Univ Sao Paulo, Dept Anal Clin Toxicol & Bromatol, Fac Ciencias Farmaceut Ribeirao Preto, BR-14049 Ribeirao Preto, SP - Brazil
[2] Univ Michigan, Sch Dent, Div Oral Pathol Med Radiol, Dept Periodont & Oral Med, Ann Arbor, MI 48109 - USA
[3] Univ Sao Paulo, Dept Quim & Fis, Fac Ciencias Farmaceut Ribeirao Preto, BR-14049 Ribeirao Preto, SP - Brazil
[4] Fac Med Sao Jose do Rio Preto, Dept Biol Mol, Sao Jose Do Rio Preto, SP - Brazil
[5] Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD - USA
Total Affiliations: 5
Document type: Journal article
Source: Molecular and Cellular Biochemistry; v. 363, n. 1-2, p. 65-74, APR 2012.
Web of Science Citations: 19
Abstract

SET protein (I2PP2A) is an inhibitor of PP2A, which regulates the phosphorylated Akt (protein kinase B) levels. We assessed the effects of SET overexpression in HEK293T cells, both in the presence and the absence of mild oxidative stress induced by 50 mu M tert-butyl hydroperoxide. Immunoblotting assays demonstrated that SET accumulated in HEK293T cells and increased the levels of phosphorylated Akt and PTEN; in addition, SET decreased glutathione antioxidant defense of cell and increased expression of genes encoding antioxidant defense proteins. Immunofluorescence analysis demonstrated that accumulated SET was equally distributed in cytoplasm and nucleus; however, in cells that had been exposed to oxidative stress, SET was found in large aggregates in the cytoplasm. SET accumulation in HEK293T cells correlated with inhibition of basal apoptosis as evidenced by a decrease in annexin V staining and activity of caspases; under mild oxidative stress, SET accumulation correlated with caspase-independent cell death, as evidenced by increased PI and annexin V/PI double staining. The results suggest that accumulated SET could act via Akt/PTEN either as cell survival signal or as oxidative stress sensor for cell death. (AU)

FAPESP's process: 05/03380-2 - SET protein in head and neck squamous cell carcinoma
Grantee:Andréia Machado Leopoldino
Support type: Scholarships abroad - Research
FAPESP's process: 06/06334-4 - Study molecular and functional of oncoprotein SET
Grantee:Andréia Machado Leopoldino
Support type: Research Grants - Young Investigators Grants
FAPESP's process: 09/52228-0 - Studies on resistance to apoptosis in cancer, head/neck model: signaling via with emphasis on PIP3-Akt/SET, oxidative stress, mitochondria and relationships
Grantee:Carlos Curti
Support type: Research Projects - Thematic Grants