title: RhoA GTPase regulates radiation-induced alterations in endothelial cell adhesion and migration.
abstract: Endothelial cells of the microvasculature are major target of ionizing radiation, responsible of the radiation-induced vascular early dysfunctions. Molecular signaling pathways involved in endothelial responses to ionizing radiation, despite being increasingly investigated, still need precise characterization. Small GTPase RhoA and its effector ROCK are crucial signaling molecules involved in many endothelial cellular functions. Recent studies identified implication of RhoA/ROCK in radiation-induced increase in endothelial permeability but other endothelial functions altered by radiation might also require RhoA proteins. Human microvascular endothelial cells HMEC-1, either treated with Y-27632 (inhibitor of ROCK) or invalidated for RhoA by RNA interference were exposed to 15Gy. We showed a rapid radiation-induced activation of RhoA, leading to a deep reorganisation of actin cytoskeleton with rapid formation of stress fibers. Endothelial early apoptosis induced by ionizing radiation was not affected by Y-27632 pre-treatment or RhoA depletion. Endothelial adhesion to fibronectin and formation of focal adhesions increased in response to radiation in a RhoA/ROCK-dependent manner. Consistent with its pro-adhesive role, ionizing radiation also decreased endothelial cells migration and RhoA was required for this inhibition. These results highlight the role of RhoA GTPase in ionizing radiation-induced deregulation of essential endothelial functions linked to actin cytoskeleton.
authors: Inserm UMR U892, Centre de Recherche en Cancérologie Nantes-Angers CRCNA, Institut de Recherche Thérapeutique IRT-UN, Université de Nantes, 8 Quai Moncousu, BP 70721, F-44007, France.
authors: Matthieu
authors: M
authors: Rousseau
authors: Marie-Hélène
authors: MH
authors: Gaugler
authors: Audrey
authors: A
authors: Rodallec
authors: Stéphanie
authors: S
authors: Bonnaud
authors: François
authors: F
authors: Paris
authors: Isabelle
authors: I
authors: Corre
mesh_terms: D000199:Actins / Q000378:metabolism; D000577:Amides / Q000494:pharmacology; D017209:Apoptosis / Q000528:radiation effects; D002448:Cell Adhesion / Q000528:radiation effects; D002460:Cell Line; D002465:Cell Movement / Q000528:radiation effects*; D003599:Cytoskeleton / Q000378:metabolism; D004730:Endothelium, Vascular / Q000201:enzymology / Q000502:physiology / Q000528:radiation effects*; D005353:Fibronectins / Q000378:metabolism; D006801:Humans; D011725:Pyridines / Q000494:pharmacology; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D000199:Actins; D000577:Amides; D005353:Fibronectins; D011725:Pyridines; C066737:RHOA protein, human; C108830:Y 27632; D054460:rho-Associated Kinases; D020742:rhoA GTP-Binding Protein