Radical scavenging compound J 811 inhibits hydrogen peroxide-induced death of cerebellar granule cells
✍ Scribed by M.E. Götz; E. Ahlbom; B. Zhivotovsky; D. Blum-Degen; M. Oettel; W. Römer; P. Riederer; S. Orrenius; S. Ceccatelli
- Publisher
- John Wiley and Sons
- Year
- 1999
- Tongue
- English
- Weight
- 186 KB
- Volume
- 56
- Category
- Article
- ISSN
- 0360-4012
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✦ Synopsis
Oxidative stress is considered to be an important pathophysiological condition to promote cell death in a broad variety of disorders, such as cardiovascular and neurodegenerative diseases. Scavestrogens, structurally derived from estradiol, are potent radical scavengers and inhibitors of iron-induced cell damage in vitro. In this study the potential cytoprotective effects of the so-called scavestrogen estra-1,3,5(10),8tetraene-3,17␣-diol, J 811, was tested using rat cerebellar granule cells (CGCs) exposed to 25 or 50 M hydrogen peroxide (H 2 O 2 ). H 2 O 2 -induced apoptotic cell death was detected by the appearance of high molecular weight DNA fragments and nuclear condensation. The addition of J 811 before or shortly after the exposure to H 2 O 2 prevented CGC apoptosis in a dose-dependent manner. The estrogen receptor antagonist ICI 182.780 failed to prevent the protective effect of J 811, suggesting that the latter is not dependent on estrogen receptor activation. The lack of protection against apoptosis caused by colchicine suggests that J 811 is neither interfering with the activation of caspase-3, nor acting downstream of caspase-3. Therefore, the protective effect observed against H 2 O 2 seems to be upstream caspases activation, pointing to a scavenging action of J 811. Thus the scavestrogen J 811 is a powerful antioxidant able to interfere with radicalmediated cell death and is potentially useful in diseases where reactive oxygen species are involved.