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AMP converted from intracellularly transported adenosine upregulates p53 expression to induce malignant pleural mesothelioma cell apoptosis.
Nogi, Yoshitaka; Kanno, Takeshi; Nakano, Takashi; Fujita, Yumiko; Tabata, Chiharu; Fukuoka, Kazuya; Gotoh, Akinobu; Nishizaki, Tomoyuki.
Afiliación
  • Nogi Y; Division of Bioinformation, Department of Physiology, Hyogo College of Medicine, Mukogawa-cho, Nishinomiya, Japan.
Cell Physiol Biochem ; 30(1): 61-74, 2012.
Article en En | MEDLINE | ID: mdl-22759956
ABSTRACT
BACKGROUND/

AIMS:

The present study investigated adenosine-induced apoptosis in human malignant pleural mesothelioma cells.

METHODS:

MTT assay, TUNEL staining, flow cytometry using propidium iodide and annexin V-FITC, real-time RT-PCR, Western blotting, and assay of caspase-3, -8, and -9 activities were carried out using malignant pleural mesothelioma cell lines such as NCI-H28, NCI-H2052, NCI-H2452, and MSTO-211H cells, and p53 or A(3) adenosine receptor was knocked-down by transfecting each siRNA into cells.

RESULTS:

Adenosine induced apoptosis in all the malignant pleural mesothelioma cells used here, independently of caspase activation. The adenosine effect was prevented by the adenosine transporter inhibitor dipyridamole, the adenosine kinase inhibitor ABT-702, or the A(3) adenosine receptor inhibitor MRS1191. Adenosine upregulated expression of the p53 mRNA and protein, that is abolished by ABT-702, but not by knocking-down A(3) adenosine receptor. Adenosine-induced apoptosis in NCI-H28 cells was significantly inhibited by knocking-down p53 and in part by knocking-down A(3) adenosine receptor.

CONCLUSION:

The results of the present study show that AMP converted from intracellularly transported adenosine upregulates p53 expression to induce caspase-independent apoptosis in malignant pleural mesothelioma cells and that A(3) adenosine receptor also participates partially in the apoptosis by the different mechanism.
Asunto(s)

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Adenosina / Regulación hacia Arriba / Adenosina Monofosfato / Proteína p53 Supresora de Tumor / Apoptosis Límite: Humans Idioma: En Revista: Cell Physiol Biochem Asunto de la revista: BIOQUIMICA / FARMACOLOGIA Año: 2012 Tipo del documento: Article País de afiliación: Japón

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Adenosina / Regulación hacia Arriba / Adenosina Monofosfato / Proteína p53 Supresora de Tumor / Apoptosis Límite: Humans Idioma: En Revista: Cell Physiol Biochem Asunto de la revista: BIOQUIMICA / FARMACOLOGIA Año: 2012 Tipo del documento: Article País de afiliación: Japón