Browsing by Subject "ERK1/2"

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    Cisplatin induced apoptosis of ovarian cancer A2780s cells by activation of ERK/p53/PUMA signals
    (Universidad de Murcia. Departamento de Biología Celular e Histología, 2018) Song, Hao; Wei, Mei; Liu, Wenfen; Shen, Shulin; Li, Jiaqun; Wang, Liming
    Cisplatin (CDDP) is one of the most effective anticancer agents widely used in the treatment of solid tumors, including ovarian cancer. It is generally considered as a cytotoxic drug which kills cancer cells by causing DNA damage, and subsequently inducing apoptosis in cancer cells. However, the underlying mechanisms leading to cell apoptosis remain obscure. In this study, the signaling pathways involved in CDDPinduced apoptosis were examined using CDDP-sensitive ovarian cancer A2780s cells. A2780s cells were treated with CDDP (1.5-3 μg/ml) for 6h, 12h and 24h. Using siRNA targeting P53 and PUMA, and a selective MEK inhibitor, PD98059 to examine the relation between ERK1/2 activation, p53 and PUMA expression after exposure to CDDP, and the effect on CDDP-induced apoptosis. The results shown that treatment of A2780s cells with CDDP (3 μg/ml) for 6-24h induced apoptosis, resulting in the activation of extracellular signalregulated kinase 1/2 (ERK1/2) and accumulation of p53 and PUMA (p53 upregulated modulator of apoptosis) protein. Knockdown of P53 or PUMA by siRNA transfection blocked CDDP-induced apoptosis. Inhibition of ERK1/2 using PD98059, a selective MEK inhibitor, blocked the apoptotic cell death but prevented CDDP-induced accumulation of p53 and PUMA. Knockdown of P53 by siRNA transfection also blocked CDDP-induced accumulation of PUMA. We therefore concluded that CDDP activated ERK1/2 and inducedp53-dependent PUMA upregulation, resulting in triggering apoptosis in A2780s cells. Our study clearly demonstrates that the ERK1/2/p53/PUMA axis is related to CDDP-induced cell death in A2780s cells.
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    The PI3K/Akt and MAPK-ERK1/2 pathways are altered in STZ induced diabetic rat placentas
    (F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2014) Ozmen, Aslı; Unek, Gozde; Kipmen-Korgun, Dijle; Turkay Korgun, Emin
    Diabetic pregnancy is associated with complications such as early and late embryonic death, fetal growth disorders, placental abnormalities, and embryonal-placental metabolic disorders. Excessive apoptosis and/or changes of proliferation mechanisms are seen as a major event in the pathogenesis of diabetesinduced embryonic death, placental weight and structural anomalies. Akt and ERK1/2 proteins are important for placental and fetal development associated with cellular proliferation and differentiation mechanisms. The mechanism underlying the placental growth regulatory effects of hyperglycemia have not been elucidated. Moreover, it is still not determined how Akt and ERK1/2 proteins related proliferation and apoptosis mechanisms are influenced by Streptozotocin (STZ) induced diabetic rat placental development. The aim of this study was to investigate the expression levels and spatio-temporal immunolocalizations of Akt, p-Akt, ERK1/2 and p-ERK1/2 proteins in normal and STZ-treated diabetic rat placental development. In order to compose the diabetic group, pregnant females were injected with a single dose of 40mg/kg STZ intraperitonally seven days before their sacrifice at 12th, 14th, 16th, 18th and 20th day of their gestation. We found that maternal diabetic environment led to a decrease in ERK1/2 and Akt phosphorylation during rat placental development. It could be said that MAPK ERK1/2 and PI3K/Akt cell signaling pathways are affected from hyperglycemic conditions in rat placentas. In conclusion, hyperglycemia-induced placental and embryonal developmental abnormalities could be associated with reduction of Akt and ERK1/2 phosphorylation.