ANG II AT2 RECEPTORS INDUCE APOPTOSIS IN HELA CELLS

MANZUR JIMENA; BERON WALTER; KOTLER MÓNICA; CIUFFO GLADYS

San Luis

Congreso; 47 Annual Meeting Argentine Society for Biochemistry and Molecular Biology; 2011

<!-- /* Font Definitions */@font-face{font-family:"ＭＳ 明朝";mso-font-charset:78;mso-generic-font-family:auto;mso-font-pitch:variable;mso-font-signature:-536870145 1791491579 18 0 131231 0;}@font-face{font-family:"Cambria Math";panose-1:2 4 5 3 5 4 6 3 2 4;mso-font-charset:0;mso-generic-font-family:auto;mso-font-pitch:variable;mso-font-signature:-536870145 1107305727 0 0 415 0;}@font-face{font-family:Cambria;panose-1:2 4 5 3 5 4 6 3 2 4;mso-font-charset:0;mso-generic-font-family:auto;mso-font-pitch:variable;mso-font-signature:-536870145 1073743103 0 0 415 0;} /* Style Definitions */p.MsoNormal, li.MsoNormal, div.MsoNormal{mso-style-unhide:no;mso-style-qformat:yes;mso-style-parent:"";margin:0cm;margin-bottom:.0001pt;mso-pagination:widow-orphan;font-size:12.0pt;font-family:Cambria;mso-fareast-font-family:"ＭＳ 明朝";mso-bidi-font-family:"Times New Roman";}.MsoChpDefault{mso-style-type:export-only;mso-default-props:yes;font-size:10.0pt;mso-ansi-font-size:10.0pt;mso-bidi-font-size:10.0pt;font-family:Cambria;mso-ascii-font-family:Cambria;mso-fareast-font-family:"ＭＳ 明朝";mso-hansi-font-family:Cambria;}@page WordSection1{size:595.0pt 842.0pt;margin:72.0pt 90.0pt 72.0pt 90.0pt;mso-header-margin:35.4pt;mso-footer-margin:35.4pt;mso-paper-source:0;}div.WordSection1{page:WordSection1;}-->The signal transduction mechanism of AngII AT receptors in tissue 2 remodeling and organogenesis remains unclear.Apoptosis is a mechanism involved in tissue differentiation. The aim of thisproject was to study apoptosis induction mediated by AT in 2 response to Ang II.HeLa cells over-expressing Ang II AT receptors 2 alone or together with RhoA WTor its mutants, were used as a  model tostudy the signaling events triggering apoptosis. Apoptosis  was evaluated by means of nuclearcondensation, F-actin  disassembly, caspases3 and 8 cleavage and caspase 3/7 activation. In HeLa-AT cells, cleavage ofcaspases 3 and 8 increased in a time 2 dependent manner after 30 minstimulation. Caspase cleavage  appearedearlier in cells co-expressing the constitutively active mutant of RhoA whilethe effect was absent in cells expressing the dominant negative RhoA N19. Wealso studied p38MAPK participation in the signaling pathway activated by AT andfound 2 that inhibition with SB203580 increased apoptosis. To characterize  the pathway, we determined JNK phosphorylationand FAK cleavage by western blot. Cleavage of FAK was time-dependent inHela-AT2 cells induced with Ang II. Co-expression of RhoA isoforms modulatesFAK cleavage. The present results support a central role of RhoA in thesignaling pathway of Ang II AT2 receptors in apoptosis induction, withparticipation of JNK, p38MAPK and FAK.