Since they have shown AND .. stated .. vegetables should be
eaten with meat .. DUE TO .. the fact meat causes oxidation
in the gut and the vegetables / antioxidants diminish this
oxidation .. would this study SHOW CLEARLY .. meat is a bad
.. thing .. ?
Am J Physiol Cell Physiol. 2004 Jun 2 [Epub ahead of print]
Related Articles, Links
Novel Effect of NF-{kappa}B Activation --Carbonylation and
Nitration Injury to The Cytoskeleton and Disruption of
Monolayer Barrier in Intestinal Epithelium.
Banan A, Zhang L, Shaikh M, Fields JZ, Farhadi A,
Keshavarzian A.
Medicine / Gastroenterology, Molecular Physiology and
Pharmacology, Rush University of Chicago, School of
Medicine, Chicago, IL, USA.
Using monolayers of intestinal cells, we reported that
upregulation of iNOS is required for oxidative injury and
that activation of NF-kappaB is key to cytoskeletal
instability. In the current study we hypothesized that NF-
kappaB activation is crucial to oxidant-induced iNOS
upregulation and its injurious consequences, cytoskeletal
oxidation & nitration and monolayer dysfunction. Wild type
(WT) cells were pretreated with inhibitors of NF-kappaB +/-
oxidant (H2O2). Other cells were transfected with an I-
kappaBalpha mutant (an inhibitor of NF-kappaB). RESULTS:
{A} Relative to WT cells exposed to vehicle, oxidant
exposure caused increases in I-kappaBalpha instability; NF-
kappaB subunits activation; iNOS-related activity [NO,
oxidative stress, tubulin nitration]; microtubule
disassembly & instability [increased monomeric & decreased
polymeric tubulin]; and monolayer disruption. {B}
Monolayers pretreated with NF-kappaB inhibitors (MG-132,
lactacystin) were protected against oxidation, showing
decreases in all measures of the NF-kappaB-->iNOS-->NO
pathway. {C} Dominant mutant stabilization of I-kappaBalpha
to inactivate NF-kappaB suppressed all measures of the
iNOS/NO upregulation while protecting monolayers against
oxidant insult. In these mutants, we found prevention of
tubulin nitration & oxidation and enhancement of
cytoskeletal and monolayer stability. CONCLUSIONS: [1] NF-
kappaB is required for oxidant-induced iNOS upregulation
and the consequent nitration and oxidation of cytoskeleton.
[2] NF-kappaB activation causes cytoskeletal injury
following upregulation of NO driven processes. [3] The
molecular event underlying the destabilizing effects of NF-
kappaB appears to be increases in carbonylation and
nitrotyrosination of the subunit components of
cytoskeleton. The ability to promote NO overproduction and
cytoskeletal nitration/oxidation is a novel mechanism not
previously attributed to NF-kappaB in cells.
PMID: 15175222 [PubMed - as supplied by publisher]
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