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Radical scavenging compound J 811 inhibits hydrogen peroxide‐induced death of cerebellar granule cells
Author(s) -
Götz M.E.,
Ahlbom E.,
Zhivotovsky B.,
BlumDegen D.,
Oettel M.,
Römer W.,
Riederer P.,
Orrenius S.,
Ceccatelli S.
Publication year - 1999
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/(sici)1097-4547(19990515)56:4<420::aid-jnr9>3.0.co;2-p
Subject(s) - apoptosis , chemistry , programmed cell death , reactive oxygen species , oxidative stress , hydrogen peroxide , caspase , estrogen receptor , microbiology and biotechnology , pharmacology , biochemistry , biology , cancer , breast cancer , genetics
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),8‐tetraene‐3,17α‐diol, J 811, was tested using rat cerebellar granule cells (CGCs) exposed to 25 or 50 μM 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. J. Neurosci. Res. 56:420–426, 1999. © 1999 Wiley‐Liss, Inc.