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Abstract:

Apoptosis plays an important role in cellular processes such as development, differentiation, and homeostasis. Although the participation of angiotensin II (Ang II) AT2 receptors (AT 2R) in cellular apoptosis is well accepted, the signaling pathway involved in this process is not well established. We evaluated the participation of signaling proteins focal adhesion kinase (FAK), RhoA, and p38 mitogen-activated protein kinase (p38MAPK) in apoptosis induced by Ang II via AT 2R overexpressed in HeLa cells. Following a short stimulation time (120 to 240 minutes) with Ang II, HeLa-AT 2 cells showed nuclear condensation, stress fibers disassembly and membrane blebbing. FAK, classically involved in cytoskeleton reorganization, has been postulated as an early marker of cellular apoptosis. Thus, we evaluated FAK cleavage, detected at early stimulation times (15 to 30 minutes). Apoptosis was confirmed by increased caspase-3 cleavage and enzymatic activity of caspase-3/7. Participation of RhoA was evaluated. HeLa-AT 2 cells overexpressing RhoA wild-type (WT) or their mutants, RhoA V14 (constitutively active form) or RhoA N19 (dominant-negative form) were used to explore RhoA participation. HeLa-AT 2 cells expressing the constitutively active variant RhoA V14 showed enhanced apoptotic features at earlier times as compared with cells expressing the WT variant. RhoA N19 expression prevented nuclear condensation/caspase activation. Inhibition of p38MAPK caused an increase in nuclear condensation and caspase-3/7 activation, suggesting a protective role of p38MAPK. Our results clearly demonstrated that stimulation of AT 2R induce apoptosis with participation of FAK and RhoA while p38MAPK seems to play a prosurvival role. © 2018 Wiley Periodicals, Inc.

Registro:

Documento: Artículo
Título:Focal adhesion kinase, RhoA, and p38 mitogen-activated protein kinase modulates apoptosis mediated by angiotensin II AT2 receptors
Autor:Manzur, M.J.; Aguilera, M.O.; Kotler, M.L.; Berón, W.; Ciuffo, G.M.
Filiación:Department of Biochemistry and Biological Sci., Universidad Nacional de San Luis, San Luis, Argentina
Instituto de Histología y Embriología, Facultad de Ciencias Médicas, Universidad Nacional de Cuyo-CONICET, Mendoza, Argentina
Laboratorio de Disfunción Celular en Enfermedades Neurodegenerativas y Nanomedicina, Departamento de Química Biológica, Instituto deQuímica Biológica Ciencias Exactas y Naturales, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina
Instituto Multidisciplinario de Investigaciones Biológicas, San Luis (IMIBIO, SL, CONICET), Argentina
Palabras clave:angiotensin II receptors; apoptotic features; caspase activation; focal adhesion kinase; RhoA/Rho-associated kinase; angiotensin 2 receptor; caspase 3; focal adhesion kinase; mitogen activated protein kinase p38; Rho kinase; RhoA guanine nucleotide binding protein; apoptosis; Article; cell differentiation; cell survival; cell viability; controlled study; enzyme activation; enzyme activity; HeLa cell line; internalization; priority journal; protein cleavage; signal transduction; stress fiber
Año:2019
Volumen:120
Número:2
Página de inicio:1835
Página de fin:1849
DOI: http://dx.doi.org/10.1002/jcb.27496
Título revista:Journal of Cellular Biochemistry
Título revista abreviado:J. Cell. Biochem.
ISSN:07302312
CODEN:JCEBD
CAS:caspase 3, 169592-56-7; RhoA guanine nucleotide binding protein; RhoB guanine nucleotide binding protein; RhoC guanine nucleotide binding protein
Registro:http://digital.bl.fcen.uba.ar/collection/paper/document/paper_07302312_v120_n2_p1835_Manzur

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Citas:

---------- APA ----------
Manzur, M.J., Aguilera, M.O., Kotler, M.L., Berón, W. & Ciuffo, G.M. (2019) . Focal adhesion kinase, RhoA, and p38 mitogen-activated protein kinase modulates apoptosis mediated by angiotensin II AT2 receptors. Journal of Cellular Biochemistry, 120(2), 1835-1849.
http://dx.doi.org/10.1002/jcb.27496
---------- CHICAGO ----------
Manzur, M.J., Aguilera, M.O., Kotler, M.L., Berón, W., Ciuffo, G.M. "Focal adhesion kinase, RhoA, and p38 mitogen-activated protein kinase modulates apoptosis mediated by angiotensin II AT2 receptors" . Journal of Cellular Biochemistry 120, no. 2 (2019) : 1835-1849.
http://dx.doi.org/10.1002/jcb.27496
---------- MLA ----------
Manzur, M.J., Aguilera, M.O., Kotler, M.L., Berón, W., Ciuffo, G.M. "Focal adhesion kinase, RhoA, and p38 mitogen-activated protein kinase modulates apoptosis mediated by angiotensin II AT2 receptors" . Journal of Cellular Biochemistry, vol. 120, no. 2, 2019, pp. 1835-1849.
http://dx.doi.org/10.1002/jcb.27496
---------- VANCOUVER ----------
Manzur, M.J., Aguilera, M.O., Kotler, M.L., Berón, W., Ciuffo, G.M. Focal adhesion kinase, RhoA, and p38 mitogen-activated protein kinase modulates apoptosis mediated by angiotensin II AT2 receptors. J. Cell. Biochem. 2019;120(2):1835-1849.
http://dx.doi.org/10.1002/jcb.27496