FAK, RhoA and p38MAPK modulates apoptosis mediated by Ang II AT2 receptors

MANZUR, MARÍA J.; AGUILERA, MILTON O; KOTLER, MÓNICA L.; BERÓN, WALTER; CIUFFO, GLADYS M

JOURNAL OF CELLULAR BIOCHEMISTRY

Wiley Periodicals, Inc.

Lugar: Nueva Jersey; Año: 2018

0730-2312

Apoptosis plays an important role in cellular processes such as development,differentiation and homeostasis. Although it is well-accepted the participation ofAng II AT2 receptors in cellular apoptosis, the signaling pathway involved in thisprocess is not well established. We evaluated the participation of signalingproteins FAK, RhoA and p38MAPK in apoptosis induced by Angiotensin II viaAT2 receptors overexpressed in HeLa cells. Following a short stimulation time(120-240 min) with Ang II, HeLa-AT2 cells showed nuclear condensation, stressfibers disassembly and membrane blebbing. Focal adhesion kinase (FAK),classically involved in cytoskeleton reorganization, has been postulated as anearly marker of cellular apoptosis. Thus, we evaluated FAK cleavage, detectedat early stimulation times (15-30 min). Apoptosis was confirmed by increasedcaspase 3 cleavage and enzymatic activity of caspase-3/7. Participation ofRhoA was evaluated. HeLa-AT2 cells over-expressing RhoA wild-type (WT) ortheir mutants, RhoA V14 (constitutively active form) or RhoA N19 (dominantnegative form) were used to explore RhoA participation. HeLa-AT2 cellsexpressing the constitutively active variant RhoAV14 showed enhancedapoptotic features at earlier times as compared to cells expressing the WTvariant. RhoA N19 expression prevented nuclear condensation /caspaseactivation. Inhibition of p38MAPK caused an increase in nuclear condensationand caspase 3/7 activation, suggesting a protective role of p38MAPK. Ourresults clearly demonstrated that stimulation of AT2 receptors induce apoptosiswith participation of FAK and RhoA while p38MAPK seems to play a prosurvivalrole.