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KMID : 0811720050090000069
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Korean Journal of Physiology & Pharmacology
2005 Volume.9 No. 0 p.69 ~ p.0
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Human Amylin-induced Apoptosis of RINm5F Islet β-cells is Associated with Increased Reactive Oxygen Species, but not Nitric Oxide or Zinc Ion
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Sim Yun-Beom
Lee Yun-Lyul
Kwon Hyeok-Yil
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Abstract
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Amylin is the major component of islet amyloid found in the pancreas of ＞90% patients with non-insulin dependent diabetes (NIDDM). The increase in the pancreatic amyloid deposits correlates with the gradual destruction of β-cells of individuals with NIDDM. However, the underlying molecular mechanism by which human amylin (hA) evokes β-cells apoptosis still remains unclear. The purpose of the present study, therefore, was to determine whether reactive oxygen species (ROS), nitric oxide and zinc ions are involved in hA-induced apoptosis in a continuous pancreatic islet β-cell line, RINm5F. hA significantly inhibited RINm5F cell proliferation and evoked apoptosis in a time- and concentration- dependent manner. The intracellular level of ROS was significantly increased in cultured RINm5F cells treated with hA. Whereas another important mediator of β-cell destruction, nitric oxide was not changed in its concentration. The hA-induced cell apoptosis and ROS production of RINm5F cells were significantly decreased in the cells pretreated with antioxidants (trolox, quercertin), or a cell-permeable superoxide dismutase fusion protein (Tat-SOD). However, zinc chelators (Ca-EDTA, TPEN) failed to affect hA-induced cell apoptosis and ROS accumulation. The intracellular accumulation of ROS and the protective effect of antioxidants on hA-induced ROS production in RINm5F cells were further conformed fluorescence analysis stained with dihydroethidium. Taken together, our results suggest that intracellular accumulation of ROS largely contributes to hA-induced apoptosis of RINm5F cells. Nitric oxide and zinc ions seem not to be involved in hA-induced β-cell apoptosis.
Source: Korean Journal of Physiology & Pharmacology.2005 Oct;9(Suppl I):S90-S90
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KEYWORD
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Amylin, β-cell apoptosis, ROS, NIDDM
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