caa a22 4500 475772733 CHVBK 20180406123622.0 cr unu---uuuuu 170329e20000501xx s 000 0 eng 10.1007/s001250051351 doi (NATIONALLICENCE)springer-10.1007/s001250051351 Contribution of adenoviral-mediated superoxide dismutase gene transfer to the reduction in nitric oxide-induced cytotoxicity on human islets and INS-1 insulin-secreting cells [Elektronische Daten] [C. Moriscot, F. Pattou, J. Kerr-Conte, M. J. Richard, P. Lemarchand, P. Y. Benhamou] Aims/hypothesis. Vulnerability of pancreatic islets to oxygen free radicals and nitric oxide contributes to islet transplantation obstacles. This susceptibility can be linked to the low expression levels of antioxidant enzymes in islets. Our aim was to investigate the effect of overexpressing Cu/Zn superoxide dismutase in human islets through a simple procedure on the cytotoxic effects of two nitric oxide donors: 3-morpholinosydnonimine (SIN-1) and S-Nitroso-N-acetyl-d,l-penicillamine (SNAP). Methods. Cultured human islets and INS-1 rat-derived insulin-secreting cells were transfected by an E1-deleted adenovirus carrying Cu/Zn SOD cDNA under the control of a cytomegalovirus (CMV) promoter (AdSOD). The viability of the cells was tested by the WST-1 assay (Roche, Indianapolis, Ind., USA). Results. The AdSOD procedure allowed SOD activity to increase by twofold to threefold for 2 to 8 days following transfection. Adenovirus-driven SOD overexpression was associated with a significant reduction of SIN-1-induced cytotoxicity on human islets (69.9 ± 10.5 % protection at 200 μmol/l and 40.5 ± 8.9 % protection at 400 μmol/l) and INS-1 cells (82.2 ± 8.8 % protection at 200 μmol/l and 31.1 ± 5.8 % protection at 400 μmol/l). Protection against increasing doses of SNAP was AdSOD dose-dependent. Transfected islets released significantly more insulin than control islets in glucose-theophyllin-stimulated conditions, without or following exposure to SNAP. Conclusions/interpretation. We thus established that adenoviral-induced overexpression of Cu/Zn SOD can be beneficial to human islet endocrine function and resistance to nitric oxide cytotoxicity. These data could be relevant for the development of new strategies aimed at preventing NO-induced beta-cell damage in an islet transplantation setting. [Diabetologia (2000) 43: 625-631] Springer-Verlag Berlin Heidelberg, 2000 Keywords Islet transplantation nationallicence nitric oxide nationallicence oxidant stress nationallicence superoxide dismutase nationallicence reactive oxygen species nationallicence adenovirus nationallicence gene transfer nationallicence Moriscot C. Institute of Structural Biology, Grenoble, France, FR aut Pattou F. UPRES 1048, Cell Culture Laboratory, University Hospital, Lille, France, FR aut Kerr-Conte J. UPRES 1048, Cell Culture Laboratory, University Hospital, Lille, France, FR aut Richard M. J. Department of Endocrinology, University Hospital, Grenoble, France, FR aut Lemarchand P. INSERM U25, Necker School of Medicine, Paris, France, FR aut Benhamou P. Y. Department of Endocrinology, University Hospital, Grenoble, France, FR aut https://doi.org/10.1007/s001250051351 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s001250051351 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Moriscot C. Institute of Structural Biology, Grenoble, France, FR aut NATIONALLICENCE 700 1- Pattou F. UPRES 1048, Cell Culture Laboratory, University Hospital, Lille, France, FR aut NATIONALLICENCE 700 1- Kerr-Conte J. UPRES 1048, Cell Culture Laboratory, University Hospital, Lille, France, FR aut NATIONALLICENCE 700 1- Richard M. J. Department of Endocrinology, University Hospital, Grenoble, France, FR aut NATIONALLICENCE 700 1- Lemarchand P. INSERM U25, Necker School of Medicine, Paris, France, FR aut NATIONALLICENCE 700 1- Benhamou P. Y. Department of Endocrinology, University Hospital, Grenoble, France, FR aut Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer