Apoptosis in Endothelial Cells by Cyclosporine

• Published in: Transplantation proceedings 2012-05, Vol.44 (4), p.982-984
• Main Authors: Hwang, E.A, Kim, H.S, Ha, E, Mun, K.C
• Format: Article
• Language: English
• Subjects: Apoptosis - drug effects; Biological and medical sciences; Blotting, Western; Caspase 3 - metabolism; Cell Proliferation - drug effects; Cell Survival - drug effects; Cells, Cultured; Cyclin-Dependent Kinase Inhibitor p27 - metabolism; Cyclosporine - toxicity; Dose-Response Relationship, Drug; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Human Umbilical Vein Endothelial Cells - drug effects; Human Umbilical Vein Endothelial Cells - pathology; Humans; Immunosuppressive Agents - toxicity; Medical sciences; Microscopy, Fluorescence; Poly(ADP-ribose) Polymerases - metabolism; Surgery; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Time Factors; Tissue, organ and graft immunology; Tumor Suppressor Protein p53 - metabolism
• ISSN: 0041-1345; 1873-2623
• DOI: 10.1016/j.transproceed.2012.01.089

Abstract Objectives The immunosuppressive drug cyclosporine (CsA) is a potent agent widely used after organ transplantations and to treat various autoimmune disorders. After using CsA, some patients suffer severe complications including renal and vascular toxicity, which are influenced by the degree of the endothelial damage. Several studies have demonstrated CsA treatment to directly induce apoptosis in several cell types. Thus, CsA may induce endothelial damage via activation of proapoptotic proteins. The present study was undertaken to investigate the effects of CsA on apoptosis of endothelial cells using human umbilical vein endothelial cells. Methods Proliferation was measured by using the Cell Counting Assay Kit after cells were exposed to CsA (0 L, 10 L, 30 L, 50 L or 100 μg/mL). Apoptotic cells were identified by fluorescence microscopy of 4′, 6-diamidino-2-phenylidole-stained nuclei. Western blot analysis was done for poly(ADP-ribose) polymerase (PARP), p27, p53 and caspase. Results Cell viability decreased dependent on the CsA concentration. CsA treatment group showed chromatin condensation and nuclear fragmentation. CsA produced a dose-dependent induction of p27 and reduction of procasapase-3. CsA treatment induced the degradation of 116-kDa PARP into an 89-kDa fragment. Conclusions CsA induced apoptosis of endothelial cells.