Hormesis response to ox-stress, from NIH!? :-)

[Muckerheide <muckerheide@MEDIAONE.NET>]

Friends,



Note this hormesis response to oxidative stress, from NIH research! The

results confirm IR biol responses.  Accepted J. Biol. Chem. 12/18.



Regards, Jim

===========



The roles of thioredoxin in protection against oxidative stress-induced

apoptosis in SH-SY5Y cells

Tsugunobu Andoh, P. Boon Chock, and Chuang Chin Chiueh



Laboratory of Clinical Science, NIMH, NIH,, Bethesda, MD 20892-1264



Corresponding Author: chiueh@helix.nih.gov



Using models of serum deprivation and 1-methyl-4-phenylpyridinium (MPP+), we

investigated mechanism by which thioredoxin (Trx) exerts its antiapoptotic

protection in human neuroblastoma cells (SH-SY5Y) and

preconditioning-induced neuroprotection. We showed that SH-SY5Y cells are

highly sensitive to oxidative stress and responsive to both extracellularly

administered and preconditioning-induced Trx. Serum deprivation and MPP+

produced an elevation in the hydroxyl radicals, malondialdehyde and

4-hydroxy-2,3-nonenal, causes the cells to undergo mitochondria-mediated

apoptosis. Trx, in the submicromolar range, blocked the observed apoptosis

via a multiphasic protection mechanism that includes the suppression of

cytochrome c release, most likely via the induction of Bcl-2, the inhibition

of procaspase-9 and procaspase-3 activation, and the elevated level of

Mn-SOD. The reduced form of Trx suppresses the serum free-induced hydroxyl

radicals, lipid peroxidation, and apoptosis indicates that H2O2 is removed

by Trx peroxidase. The participation of Trx in the preconditioning-induced

neuroprotection is supported by the observation that inhibition of Trx

synthesis with antisense oligonucletoides or of Trx reductase drastically

reduced the hormesis effect. This effect of Trx-mediated hormesis against

oxidative stress-induced apoptosis is striking. It induced a 30-fold shift

in LD50 in the MPP+-induced neurotoxicity.



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