Mesothelioma and Iron

"Phytic acid blocks asbestos-induced p53 activation"

That would be my free bisphosphonate again.
http://tinyurl.com/2au4yx

P53 mediates amosite asbestos-induced alveolar epithelial cell
mitochondria-regulated apoptosis. Apr 2006
Vijayalakshmi Panduri,Sailesh Surapureddi,Saul Soberanes,Sigmund A
Weitzman,Navdeep Chandel,David W Kamp
Asbestos causes pulmonary toxicity in part by generating reactive
oxygen species that cause DNA damage.
We previously showed that the mitochondria-regulated (intrinsic) death
pathway mediates alveolar epithelial cell (AEC) DNA damage and
apoptosis.
Because p53 regulates the DNA damage response in part by inducing
intrinsic cell death, we determined whether p53-dependent
transcriptional activity mediates asbestos-induced AEC mitochondrial
dysfunction and apoptosis.
We show that inhibitors of p53-dependent transcriptional activation
(pifithrin and type 16-E6 protein) block asbestos-induced AEC
mitochondrial membrane potential change (DeltaPsim), caspase 9
activation, and apoptosis.
We demonstrate that asbestos activates p53 promoter activity, mRNA
levels, protein expression, and Bax and p53 mitochondrial
translocation.
Further, pifithrin, E6, phytic acid, or rho(0)-A549 cells (cells
incapable of mitochondrial reactive oxygen species production) block
asbestos-induced p53 activation.
Finally, we show that asbestos augments p53 expression in cells at the
bronchoalveolar duct junctions of rat lungs and that phytic acid
prevents this.
These data suggest that p53-dependent transcription pathways mediate
asbestos-induced AEC mitochondria-regulated apoptosis.
This suggests an important interactive effect between p53 and the
mitochondria in the pathogenesis of asbestos-induced pulmonary
toxicity that may have broader implications for our understanding of
pulmonary fibrosis and lung cancer.


Who loves ya.
Tom


Jesus Was A Vegetarian!
http://jesuswasavegetarian.7h.com


Man Is A Herbivore!
http://tinyurl.com/a3cc3


DEAD PEOPLE WALKING
http://tinyurl.com/zk9fk

On Mar 19, 12:02*pm, ironjustice <teamtan...@hotmail.com> wrote: That
would be my free bisphosphonate again.http://tinyurl.com/2au4yx

"Strongly suggest that iron plays an important role"

Role of iron in inactivation of epidermal growth factor receptor after
asbestos treatment of human lung and pleural target cells. May 2005
Aleksander Baldys,Ann E Aust
Although the mechanism by which asbestos causes cancer remains
unknown, iron associated with asbestos is thought to play a role in
the pathogenic effects of fibers.
Here, we examined the effects of asbestos on the epidermal growth
factor receptor (EGFR) in human lung epithelial (A549) cells, human
pleural mesothelial (MET5A) cells, and normal human small airway
epithelial (SAEC) cells. Treatment of A549, MET5A, and SAEC cells with
asbestos caused a significant reduction of EGFR tyrosine
phosphorylation.
This was both time- (15 min to 24 h) and concentration-dependent (1.5,
3, and 6 mug/cm(2)) in A549 cells.
Also, treatment with 6 mug/cm(2) crocidolite for 24 h diminished the
phosphorylation levels of human EGFR 2 (HER2). Exposure of A549 cells
to 6 mug/cm(2) crocidolite for 3-24 h resulted in no detectable Y1045
phosphorylation and no apparent degradation of the EGFR. Inhibition of
fiber endocytosis resulted in a considerable inhibition of EGFR
dephosphorylation.
Removal of iron from asbestos by desferrioxamine B or phytic acid
inhibited asbestos-induced decreases in EGFR phosphorylation.
The effects of crocidolite, amosite, and chrysotile on the EGFR
phosphorylation state appeared to be directly related to the amount of
iron mobilized from these fibers.
These results strongly suggest that iron plays an important role in
asbestos-induced inactivation of EGFR.


Who loves ya.
Tom


Jesus Was A Vegetarian!
http://jesuswasavegetarian.7h.com


Man Is A Herbivore!
http://tinyurl.com/a3cc3


DEAD PEOPLE WALKING
http://tinyurl.com/zk9fk

> "Phytic acid blocks asbestos-induced p53 activation"
>
> That would be my free bisphosphonate again.http://tinyurl.com/2au4yx
>
> P53 mediates amosite asbestos-induced alveolar epithelial cell
> mitochondria-regulated apoptosis. Apr 2006
> Vijayalakshmi Panduri,Sailesh Surapureddi,Saul Soberanes,Sigmund A
> Weitzman,Navdeep Chandel,David W Kamp
> Asbestos causes pulmonary toxicity in part by generating reactive
> oxygen species that cause DNA damage.
> We previously showed that the mitochondria-regulated (intrinsic) death
> pathway mediates alveolar epithelial cell (AEC) DNA damage and
> apoptosis.
> Because p53 regulates the DNA damage response in part by inducing
> intrinsic cell death, we determined whether p53-dependent
> transcriptional activity mediates asbestos-induced AEC mitochondrial
> dysfunction and apoptosis.
> We show that inhibitors of p53-dependent transcriptional activation
> (pifithrin and type 16-E6 protein) block asbestos-induced AEC
> mitochondrial membrane potential change (DeltaPsim), caspase 9
> activation, and apoptosis.
> We demonstrate that asbestos activates p53 promoter activity, mRNA
> levels, protein expression, and Bax and p53 mitochondrial
> translocation.
> Further, pifithrin, E6, phytic acid, or rho(0)-A549 cells (cells
> incapable of mitochondrial reactive oxygen species production) block
> asbestos-induced p53 activation.
> Finally, we show that asbestos augments p53 expression in cells at the
> bronchoalveolar duct junctions of rat lungs and that phytic acid
> prevents this.
> These data suggest that p53-dependent transcription pathways mediate
> asbestos-induced AEC mitochondria-regulated apoptosis.
> This suggests an important interactive effect between p53 and the
> mitochondria in the pathogenesis of asbestos-induced pulmonary
> toxicity that may have broader implications for our understanding of
> pulmonary fibrosis and lung cancer.
>
> Who loves ya.
> Tom
>
> Jesus Was A Vegetarian!http://jesuswasavegetarian.7h.com
>
> Man Is A Herbivore!http://tinyurl.com/a3cc3
>
> DEAD PEOPLE WALKINGhttp://tinyurl.com/zk9fk