Adenovirus-mediated catalase gene transfer reduces oxidant stress in human, porcine and rat pancreatic islets

Benhamou, Pierre Yves; Moriscot, Christine; Richard, M J; Béatrix, Olivier; Badet, Lionel; Pattou, François; Kerr–Conte, Julie; Chroboczek, Jadwiga; Lemarchand, Patricia; Halimi, Serge

doi:10.1007/s001250051035

Cited by 122 publications

(71 citation statements)

References 43 publications

(29 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Still, both human and rat-derived INS-1 cells gain a significant protection by SOD transfection as it was already shown with catalase, meaning that shifting the defense systems may be sufficient. This study strengthens our previous work in which we established that adenoviral-driven catalase overexpression reduced the cytotoxicity of superoxide donors on human, porcine and rat islets [14]. Thus, adenoviral transfection of catalase and Cu/ZnSOD possibly has synergistic effects.…”

Section: Discussionsupporting

confidence: 89%

“…It is noteworthy that human islets express higher SOD or catalase activity than rodent or porcine islets [14]. It can be speculated that this plays a part in the differential susceptibility of human and rodent islets to cytokine cytotoxicity.…”

Section: Discussionmentioning

confidence: 99%

“…We therefore transfected human islets with recombinant adenovirus vectors, which are potential candidates for gene transfer trials in humans. We have established previously that adenoviral-driven catalase overexpression reduced the cytotoxicity of superoxide donors on human, porcine and rat islets [14]. This time we examined the effect of adenoviral-mediated SOD gene transfer in human islets and rat-derived insulin-secreting INS-1 cells on the cytotoxicity induced by nitric oxide donors.…”

mentioning

confidence: 98%

See 2 more Smart Citations

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

et al. 2000

Self Cite

View full text Add to dashboard Cite

It has been established from numerous studies that oxygen and nitrogen free radicals can contribute to the islet beta-cell destruction in Type I (insulin-dependent) diabetes mellitus models [1±2]. The deleterious actions of activated mononuclear cells could be mediated by cytokines through an increase in the intracellular generation of superoxide anions, nitric oxide (NO) and peroxynitrite [3±5]. Islet beta cells appear to have an exquisite sensitivity to these radicals because of constitutively low expression of antioxidant enzymes [6±7]. Several reports explained the rationale of increasing antioxidant enzyme expression Diabetologia (2000) AbstractAims/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,lpenicillamine (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 mmol/l and 40.5 ± 8.9 % protection at 400 mmol/l) and INS-1 cells (82.2 ± 8.8 % protection at 200 mmol/l and 31.1 ± 5.8 % protection at 400 mmol/l). Protection against increasing doses of SNAP was AdSOD dose-dependent. Transfected islets released significantly more insulin than control islets in glucose-theophyllinstimulated 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] Keywords Islet transplantation, nitric oxide, oxidant stress, superoxide dismutase, reactive oxygen species, adenovirus, gene transfer. Corresponding author: Dr P. Y. Benhamou, Department of Endocrinology, CHU, BP 217X, 38 043 Grenoble, France Abbreviations: AdSOD, Adenovirus-driven superoxide dismutase; IEQ, equivalent number of islets; MOI, multiplicity of infection; NO, nitric oxide; pfu, plaque-forming units; ROS, reactive oxygen species; SIN-1, 3-Morpholino sydnonimine.HCl; SNAP, S-Nitroso-N-acetyl-d,l-penicillamine; SOD, superoxide dismutase.

show abstract

Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 98%

See 1 more Smart Citation

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

et al. 2000

Self Cite

View full text Add to dashboard Cite

show abstract

“…We achieved the infection of all islets and of 30% of the islet cells, an infection rate which is well within the limits described in the literature [36]. It is important to note that since IL1RN is secreted and exerts a paracrine effect on neighbouring beta cells, it was active on more islet cells than just those infected by the adenovirus [20].…”

Section: Discussionsupporting

confidence: 79%

Adenoviral overproduction of interleukin-1 receptor antagonist increases beta cell replication and mass in syngeneically transplanted islets, and improves metabolic outcome

et al. 2007

View full text Add to dashboard Cite

show abstract

“…Recent observations show that such approaches may be feasible as adenovirally mediated catalase gene transfer to human and porcine islets in vitro reduced the effects of oxidant stress. 52 A potentially important area of study that requires further definition is the compatibility between gene delivery vehicles and preservation solutions, as it is anticipated that any gene engineering of the donor organ or tissue will be performed in solution immediately following organ procurement before reperfusion. …”

Section: Endothelial Cell Leukocytementioning

confidence: 99%

Gene therapy in transplantation

1999

View full text Add to dashboard Cite

Adenovirus-mediated catalase gene transfer reduces oxidant stress in human, porcine and rat pancreatic islets

Cited by 122 publications

References 43 publications

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

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

Adenoviral overproduction of interleukin-1 receptor antagonist increases beta cell replication and mass in syngeneically transplanted islets, and improves metabolic outcome

Gene therapy in transplantation

Contact Info

Product

Resources

About