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

Autor(es)

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]

Afiliação do(s) autor(es)

^[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

• Tipo de documento: Artigo Científico
• Fonte: Molecular and Cellular Biochemistry; v. 363, n. 1-2, p. 65-74, APR 2012.
• Citações Web of Science: 19

Resumo

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)

• Processo FAPESP: 05/03380-2 - Investigação da proteína SET em carcinoma de célula escamosa de cabeça e pescoço
• Beneficiário: Andréia Machado Leopoldino
• Modalidade de apoio: Bolsas no Exterior - Pesquisa
• Processo FAPESP: 09/52228-0 - Estudos da resistência à apoptose no câncer, modelo cabeça/pescoço: vias de sinalização com ênfase na PIP3-AKT/SET, estresse oxidativo, mitocôndria e correlações
• Beneficiário: Carlos Curti
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 06/06334-4 - Estudo molecular e funcional da oncoproteína SET
• Beneficiário: Andréia Machado Leopoldino
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores