Sensitivity of human pancreatic islets to peroxynitrite‐induced cell dysfunction and death

FEBS Letters

Bouwens, Luc¹  Hellman, Björn²  Vaghef, Hamid²  Delaney, Carol A.³  Tyrberg, Björn³  Eizirik, Décio L.³ 

[1] Laboratory of Experimental Pathology, Vrije Universiteit Brussel, Brussels, Belgium;Department of Occupational and Environmental Medicine and Department of Toxicology, Uppsala University, Uppsala, Sweden;Department of Medical Cell Biology, Uppsala University, Biomedicum, Box 571, S-751 23 Uppsala, Sweden

关键词: Peroxynitrite;    Nitric oxide;    Islets of Langerhans;    Apoptosis;    DNA damage;    Comet assay;   

DOI  :  10.1016/0014-5793(96)00977-5

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Nitric oxide and peroxynitrite (generated by the reaction of nitric oxide with the superoxide anion) may both be mediators of β-cell damage in early insulin-dependent diabetes mellitus. We observed that acute exposure of primary cultured human pancreatic islets to peroxynitrite results in a significant decrease in glucose oxidation and islet retrieval. DNA strand breaks in single human and rat islet cells are detectable after acute peroxynitrite exposure, followed by a decrease in islet cell survival after 1 h and 24 h. Cell death appeared to occur via a toxic cell death mechanism (necrosis) rather than apoptosis, as suggested by vital staining and ultrastructural evidence of early membrane and organelle degradation, mitochondrial swelling and loss of matrix. This study demonstrates for the first time that cultured human pancreatic islets are susceptible to the noxious effects of peroxynitrite.

【 授权许可】

Unknown