백서 조골세포주에서의 싸이클로스포린 산소유리기 유도능 = The Ability of Cyclosporine (CsA) to Induce Oxigen Free Radicals in a Rat Osteoblast Cell Line

다국어 초록 (Multilingual Abstract)

Objectives: This study examined the ability of Cyclosporine (CsA) to induce apoptosis in a rat osteoblast cell line.
Methods: Rat osteoblast ROS 17/2.8 cells were cultured, and treated with with 0.1～40μg/mL CsA for 24 hours after plating of cells. Cell viability was determined by the MTT assay. Western Blot Analysis was done with primary antibodies to caspase-3 and caspase-8. Reactive oxygen species (ROS) synthesis was measured by flowcytometry.
Results: Cell viability decreased in dose-dependent manner with increasing concentrations of CsA. Treatment of ROS 17/2.8 cells with 0.1, 0.5, 1, 5, 10, 20, or 40 μg/mLg/mL CsA caused 85%, 80%, 73%, 60%, 45%, 40%, and 27% cell viability, respectively. Western blot analysis showed reduced caspase-3 expression and induced caspase-8. The ROS in a dose-and time-dependent manner were increased by CsA.
Conclusion: These results suggest that CsA can induce oxygen free radicals which appears to trigger apoptosis by activating pro-apoptotic signals. CsA plays a role in the post- transplatation bone diseases via the induction of apoptosis in osteoblast.

참고문헌 (Reference)

1 Ishikawa Y, "c-Jun/AP-1, but not NF-kappa B, is a mediator for oxidantinitiated apoptosis in glomerular mesangial cells" 240 : 496-501, 1997

2 Borel JF, "The history of cyclosporin A and its significance, In: Cyclosporin A" Elsevier. Biomdical Press 5-17, 1982

3 Schlosberg M, "The effect of cyclosporin A administration and its withdrawal on bone mineral metabolism in the rat" 124 : 2179-2184, 1989

4 Rodan GA, "The cells of bone. In: Osteoporosis; etiology, diagnosis, and management. 2nd ed" Lippincott-Raven 1-39, 1995

5 Fornoni A, "Striker GE, Striker LJ. Cyclosporin A affects extracellular matrix synthesis and degradation by mouse MC3T3-E1 osteoblasts in vitro" 16 : 500-505, 2001

6 Matés JM, "Role of reactive oxygen species in apoptosis: implications for cancer theraphy" 32 : 157-170, 2000

7 Halliwell B, "Role of free radicals and catalytic metal ions in human disease: an overview" 186 : 1-85, 1990

8 Gabai VL, "Role of Hsp70 in regulation of stress-kinase JNK: implications in apoptosis and aging" 438 : 1-4, 1998

9 Harrison JH, "Renal homotransplantation in identical twins" 6 : 432-436, 1956

10 Sugiyama H, "Reactive oxygen species induce apoptosis in cultured human mesangial cells" 7 : 2357-2363, 1996

11 Evan GI, "Proliferation, cell cycle and apoptosis in cancer" 411 : 342-348, 2001

12 Katz IA, "Posttransplantation bone disease" 7 : 123-126, 1992

13 Toledano BJ, "Platelet-activating factor abrogates apoptosis induced by cross-linking of the surface IgM receptor in a human B lymphoblastoid cell line" 15 : 3705-3715, 1997

14 Satyanarayana PS, "Oxidative stressmediated renal dysfunction by cyclosporine A in rats: attenuation by trimetazidine" 24 : 259-274, 2002

15 Buttke TM, "Oxidative stress as a mediator of apoptosis" 15 : 7-10, 1994

16 Redondo-Horcajo M, "Oxidative and nitrosative stress in kidney disease: a case for cyclosporine A" 18 : 453-457, 2005

17 Shane E, "Osteoporosis after cardiac transplantation" 94 : 257-264, 1993

18 Epstein S, "Organ transplantation and osteoporosis" 7 : 255-261, 1995

19 Bojes HK, "Nuñ1ez G, et al. Bcl-xL overexpression attenuates glutathione depletion in FL5.12 cells following interleukin-3 withdrawal" 325 : 115-119, 1997

20 Olyaei AJ, "Nephrotoxicity of immunosuppressive drugs: new insight and preventive strategies" 7 (7): 384-389, 2001

21 Green DR, "Mitochondria and apoptosis" 281 : 1309-1312, 1998

22 Guo CY, "Mechanism of bone loss after cardiac transplantation" 22 : 267-271, 1998

23 Kamesaki H, "Mechanism involved in chemotherapyinduced apoptosis and their implications in cancer chemotherapy" 68 : 29-43, 1998

24 Weinstein RS, "Inhibition of osteoblastogenesis and promotion of apoptosis of osteoblasts and osteocytes by glucocorticoids. Potential mechanisms of their deleterious effects on bone" 102 : 274-282, 1998

25 KaramehićJ, "Hepatotoxicity of cyclosporine in patients with kidney transplants" 53 : 193-195, 1999

26 Anderson KM, "Free radicals and reactive oxygen species in programmed cell dath" 52 : 451-463, 1999

27 Kawakami A, "Fas and Fas ligand interaciton is necessary for human osteoblast apoptosis" 12 : 1637-1646, 1997

28 Silvestrini G, "Evaluation of apoptosis and the glucocorticoid receptor in the cartilage growth plate and metaphyseal bone cells of rats after high-dose treatment with corticosterone" 26 : 33-42, 2000

29 Bennett WM, "Cyclosporine-associated hypertension" 85 : 131-133, 1988

30 Derici U, "Cyclosporine-A induced neurotoxicity after renal transplantation" 101 : 124-127, 2001

31 Movsowitz C, "Cyclosporin-A in vivo produces severe osteopenia in the rat: effect of dose and duration of administration" 123 : 2571-2577, 1998

32 Calne RY, "Cyclosporin A initially as the only immunosuppressant in 34 recipients of cadaveric organs: 32 kidneys, 2 pancreases, and 2 livers" 17 : 1033-1036, 1979

33 Calne RY, "Cyclosporin A in patients receiving renal allografts from cadaver donors"

34 Kitajima I, "Ceramide induced AP-1 activation is a mediator of apoptotic response to TNF-a in periarticular osteoblasts in patients with rheumatoid arthritis" 78-, 1997

35 Wyllie AH, "Cell death: the significance of apoptosis" 68 : 251-306, 1980

36 Vaux DL, "Cell death in development" 96 : 245-254, 1999

37 Cohen GM, "Caspases: the executioners of apoptosis" 326 : 1-16, 1997

38 Hockenbery DM, "Bcl-2 functions in an antioxidant pathway to prevent apoptosis" 75 : 241-251, 1993