WR-1065 and Radioprotection of Vascular Endothelial Cells. II. Morphology

• Published in: Radiation research 1996-02, Vol.145 (2), p.217-224
• Main Authors: Mooteri, S. N., Podolski, J. L., Drab, E. A., Saclarides, T. J., Onoda, J. M., Kantak, S. S., Rubin, D. B.
• Format: Article
• Language: English
• Subjects: Actin Cytoskeleton - drug effects; Actin Cytoskeleton - radiation effects; Actin Cytoskeleton - ultrastructure; Actins; Actins - chemistry; Animals; Biological and medical sciences; Biological effects of radiation; Cattle; Cell Cycle - drug effects; Cell Cycle - radiation effects; Cell Movement - drug effects; Cell Movement - radiation effects; Cells, Cultured; Cultured cells; Cytoskeleton; Disulfides; Disulfides - chemistry; DNA damage; Endothelial cells; Endothelium, Vascular - drug effects; Endothelium, Vascular - radiation effects; Fundamental and applied biological sciences. Psychology; Integrins; Irradiation; Mercaptoethylamines - pharmacology; Microfilaments; Radiation-Protective Agents - pharmacology; Radioprotection; Receptors, Fibronectin - metabolism; Stress fibers; Tissues, organs and organisms biophysics; Up-Regulation - drug effects; Up-Regulation - radiation effects; Wound Healing - radiation effects
• ISSN: 0033-7587; 1938-5404
• DOI: 10.2307/3579177

Although the aminothiol WR-1065 protects normal tissues, its direct effect on the damage and restoration of the vascular endothelium is not clear. In endothelial cells, WR-1065 attenuates both the DNA damage and the G1-phase arrest induced by radiation. After the destruction of nearby endothelial cells, the survivors rearrange their cytoskeleton, migrate and replicate. To determine the effect of radiation on morphology and migration, portions of bovine aortic endothelial cell cultures were denuded with a pipette tip and irradiated (137 Cs γ rays). The following observations were noted after 5 Gy: within 10 min, there was increased formation of protein-mixed disulfides including actin-mixed disulfide; after 30 min, α 5β 1, the integrin receptor for fibronectin, was up-regulated on the apical membrane surface. Within 5 h, actin-containing stress fibers reorganized, although there was no change in the total filamentous (F-)actin content within the cells. Compared to controls after 24 h, the irradiated cells had migrated 15% farther (P < 0.01), and at the leading edge covered twice the surface area (P < 0.0001). The addition of 2 mM WR-1065 for 2 h before 5 Gy inhibited the increased expression of α 5β 1, promoted retention of stress fibers and prevented the enhanced cell migration and spreading. These results indicate that WR-1065 prevents radiation-induced morphological responses. This effect appears to be mediated by an impact on both adhesion molecule expression and cytoskeletal reorganization.