Can someone translate the implications of this abstract? I appreciate
that it was posted by ForrestsMom, and it sounds like it is filled with
vital information, but I cannot make heads or tails of it.
--Bob
CG for Bill (83/10+)
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Title: Prevention of dopamine-induced cell death by thiol antioxidants:
possible implications for treatment of Parkinson's disease.
Title Abreviation: Exp Neurol Date of Pub: 1996 Sep
Author: Offen D; Ziv I; Sternin H; Melamed E; Hochman A;
Issue/Part/Supplement: 1 Volume Pagination: 32-9
Issue: 141
MESH Headings: Acetylcysteine (*PD); Animal; Antioxidants (PD);
Apoptosis
(*DE); Dithiothreitol (*PD); Dopamine (*PD); Glutathione (*PD);
Neuroprotective Agents (PD); Parkinson Disease (*DT); PC12 Cells (DE);
Rats; Sulfhydryl Compounds (PD); Support, Non-U.S. Gov't; -RN-;
Journal Title Code: EQF Publication Type: JOURNAL ARTICLE
Date of Entry: 961112N Entry Month: 9701
Country: UNITED STATES Index Priority: 1
Language: Eng Unique Identifier: 96390692
Unique Identifier:
96390692 ISSN: 0014-4886
Abstract: We have recently shown that dopamine (DA) can trigger
apoptosis,
an active program of cellular self-destruction, in various neuronal
cultures and proposed that inappropriate activation of apoptosis by DA
and
or its oxidation products may initiate nigral cell loss in Parkinson's
disease (PD). Since DA toxicity may be mediated via generation of
oxygen-free radical species, we examined whether DA-induced cell death
in
PC12 cells may be inhibited by antioxidants. We have found that the
thiol
containing compounds, reduced glutathione (GSH), N-acetyl-cysteine
(NAC),
and dithiothreitol (DTT) were markedly protective, while vitamins C and
E
had lesser or no effect. The thiol antioxidants and vitamin C but not
vitamin E, prevented dopamine autooxidation and production of
dopamine-melanin. Their protective effect has also manifested by
inhibiting DA-induced apoptosis; DNA fragmentation was prevented as was
shown histochemically by the in situ end-labeled DNA technique (TUNEL).
Intracellular GSH and other thiols constitute an important natural
defense
against oxidative stress. We have found that depletion of cellular GSH
by
the addition of phoron, a substrate of glutathione transferase, and
buthionine sulfoximine (BSO), an inhibitor of gamma-glutamyl
transpeptidase, significantly enhanced DA toxicity. Cotreatment with
NAC
rescued the cells from the toxic effect of BSO+DA, and phoron+ DA,
while
addition of GSH provided only partial protection from BSO+DA toxicity.
Our
data indicate that the thiol family of antioxidants, but not vitamins C
and E, are highly effective in rescuing cells from DA-induced
apoptosis.
Further study of the mechanisms underlying the unique protective
capacity
of thiol antioxidants may lead to the development of new
neuroprotective
therapeutic strategies for PD.
Abstract By: Author
Address: Department of Neurology, Beilinson Medical Center,
Petah-Tiqva,
Israel.
