Protein tyrosine phosphatase alpha regulates cell detachment and cell death profiles induced by nitric oxide donors in the A(431) human carcinoma cell line

Autor(es)

da Costa, Paulo E. ^[1] ; Batista, Wagner L. ^[2] ; Curcio, Marli F. ^[3] ; Moraes, Miriam S. ^[3] ; Borges, Roberta Eller ^[1] ; Nascimento, Patricia A. ^[3] ; Travassos, Luiz R. ^[4] ; Monteiro, Hugo P. ^[3]

Afiliação do(s) autor(es)

^[1] Univ Fed Sao Paulo, Dept Clin Med, BR-04044020 Sao Paulo - Brazil

^[2] Univ Fed Sao Paulo, Dept Biol Sci, BR-04044020 Sao Paulo - Brazil

^[3] Univ Fed Sao Paulo, Dept Biochem Mol Biol, Ctr Cellular & Mol Therapy CTCMol, BR-04044020 Sao Paulo - Brazil

^[4] Univ Fed Sao Paulo, Dept Microbiol Immunol & Parasitol, Expt Oncol Unit UNONEX, BR-04044020 Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Redox Report; v. 16, n. 1, p. 27-37, JAN 2011.
• Citações Web of Science: 7

Resumo

We investigated the role of protein tyrosine phosphatase-alpha (PTP alpha) expression in the cell death profile of the A431 human carcinoma cell line that was induced by cytotoxic concentrations of the nitric oxide (NO) donors sodium nitroprusside (SNP) and 3,3-bis-(aminoethyl)-1-hydroxy-2-oxo-1-triazene (NOC-18). Both NO donors promoted extensive cell detachment in A431 parental cells as compared to the detachment observed for A431 cells that ectopically expressed PTP alpha (A431 (A27B(PTP alpha)) cells). The NO-induced cell death characteristics for both cell lines were examined. After incubation for 10 hours with 2.0 mM SNP, attached or detached A431 cells underwent apoptosis. Cells were highly positive for Annexin-V, featured increased cleavage of procaspase-8, activation of downstream caspase-3, and activation of poly-ADP-ribose polymerase 1 (PARP-1). In contrast, exposure of A431 (A27B(PTP alpha)) cells to 2.0 mM SNP produced an increase in the release of lactate dehydrogenase and enhanced incorporation of propidium iodide. In addition, A431 (A27B(PTP alpha)) cells showed partial inhibition of the activities of caspase-8, caspase-3, and PARP-1 upon detachment and cell death induced by SNP treatment. Results indicate that necrotic cell damage was induced, characterized by cellular swelling and lysis. We conclude from these results that PTP alpha regulates the A431 tumor cell death profile mediated by NO donors. Expression of PTP alpha or its absence may determine the occurrence of NO-induced cell death with necrotic or apoptotic features, respectively. (AU)

• Processo FAPESP: 06/56311-0 - Estudo dos efeitos do óxido nítrico sobre a atividade sinalizadora de Src quinase em linhagens celulares que expressam ou não a proteína tirosina fosfatase alfa (PTPalfa)
• Beneficiário: Hugo Pequeno Monteiro
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 07/59617-6 - Estudos da compartimentalização celular da proteína G de baixo peso molecular Ras e da proteína antioxidante tiorredoxina sob estímulo de fontes geradoras de óxido nítrico
• Beneficiário: Hugo Pequeno Monteiro
• Modalidade de apoio: Auxílio à Pesquisa - Regular