2024-03-28T09:29:01Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/727622020-08-12T10:56:01Zcom_10261_39com_10261_1col_10261_292
Secreted phospholipase A2-IIA modulates key regulators of proliferation on astrocytoma cells
Martín, Rubén
Hernández, Marita
Ibeas, Elvira
Fuentes, Lucía
Salicio, Veronica
Arnés, Mercedes
Nieto, María Luisa
Ministerio de Ciencia y Tecnología (España)
Junta de Castilla y León
European Commission
Consejo Superior de Investigaciones Científicas (España)
Human group IIA secreted phospholipase A2 (sPLA2-IIA) has been characterized in numerous inflammatory and neoplastic conditions. sPLA2-IIA can either promote or inhibit cell growth depending on the cellular type and the specific injury. We have previously demonstrated that exogenous sPLA2-IIA, by engagement to a membrane structure, induces proliferation and activation of mitogen-activated protein kinases cascade in human astrocytoma cells. In this study, we used human astrocytoma 1321N1 cells to investigate the key molecules mediating sPLA2-IIA-induced cell proliferation. We found that sPLA2-IIA promoted reactive oxygen species (ROS) accumulation, which was abrogated in the presence of allopurinol and DPI, but not by rotenone, discarding mitochondria as a ROS source. In addition, sPLA2-IIA triggered Ras and Raf-1 activation, with kinetics that paralleled ERK phosphorylation, and co-immunoprecipitation assays indicated an association between Ras, Raf-1 and ERK. Additionally, Akt, p70 ribosomal protein S6 kinase, and S6 ribosomal protein were also phosphorylated upon sPLA2-IIA treatment, effect that was abrogated by N-acetylcysteine or LY294002 treatment indicating that ROS and phosphatidylinositol 3 kinase are upstream signaling regulators. As the inhibitors N-acetylcysteine, PD98059, LY294002 or rapamycin blocked sPLA 2-IIA-induced proliferation without activation of the apoptotic program, we suggest that inhibition of these intracellular signal transduction elements may represent a mechanism of growth arrest. Our results reveal new potential targets for therapeutic intervention in neuroinflammatory disorders and brain cancer in particular. © 2009 International Society for Neurochemistry.
2013-03-22T12:18:36Z
2013-03-22T12:18:36Z
2009
2013-03-22T12:18:36Z
artículo
Journal of Neurochemistry 111(4): 988-999 (2009)
http://hdl.handle.net/10261/72762
10.1111/j.1471-4159.2009.06377.x
http://dx.doi.org/10.13039/501100006280
http://dx.doi.org/10.13039/501100000780
http://dx.doi.org/10.13039/501100003339
http://dx.doi.org/10.13039/501100014180
eng
Postprint
openAccess
Wiley-Blackwell