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Oxidative Stress-activated JNK
Oxidative Stress-activated JNK
Hydrogen peroxide promotes Abeta production through JNK-dependent
activation of gamma -secretase.
Shen C, Chen Y, Liu H, Zhang K, Zhang T, Lin A, Jing N
J Biol Chem 2008 Apr 23.
Accumulation of senile plaques composed of amyloid beta-peptide
(Abeta) is a pathological hallmark of Alzheimer's disease (AD), and
Abeta is generated through the sequential cleavage of amyloid
precursor protein (APP) by beta- and gamma-secretase. Although
oxidative stress has been implicated in AD pathogenesis by inducing
Abeta production, the underlying mechanism remains elusive. Here we
show that the pro-oxidant hydrogen peroxide (H2O2) promotes Abeta
production through c-Jun N-terminal kinase (JNK)-dependent activation
of gamma-secretase. Treatment with H2O2 induced significant increase
in the levels of intracellular and secreted Abeta in human
neuroblastoma SH-SY5Y cells. While gamma-secretase-mediated cleavage
of APP or C99 was enhanced upon H2O2 treatment, expression of APP or
its alpha-/beta-secretase-mediated cleavage was not affected.
Silencing of the stress-activated JNK by siRNA or the specific JNK
inhibitor SP600125 reduced H2O2-induced gamma-secretase-mediated
cleavage of APP. JNK activity was augmented in human brain tissues
from AD patients, and active JNK located surrounding the senile
plaques in the brain of AD model mouse. Our data suggest that
oxidative stress-activated JNK may contribute to senile plaques
expansion through the promotion of gamma-secretase-mediated APP
cleavage and Abeta production.
The Journal of biological chemistry [J Biol Chem]
--------------------------------------------------------------------------------
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Hydrogen peroxide promotes Abeta production through JNK-dependent
activation of gamma -secretase.
Shen C, Chen Y, Liu H, Zhang K, Zhang T, Lin A, Jing N
J Biol Chem 2008 Apr 23.
Accumulation of senile plaques composed of amyloid beta-peptide
(Abeta) is a pathological hallmark of Alzheimer's disease (AD), and
Abeta is generated through the sequential cleavage of amyloid
precursor protein (APP) by beta- and gamma-secretase. Although
oxidative stress has been implicated in AD pathogenesis by inducing
Abeta production, the underlying mechanism remains elusive. Here we
show that the pro-oxidant hydrogen peroxide (H2O2) promotes Abeta
production through c-Jun N-terminal kinase (JNK)-dependent activation
of gamma-secretase. Treatment with H2O2 induced significant increase
in the levels of intracellular and secreted Abeta in human
neuroblastoma SH-SY5Y cells. While gamma-secretase-mediated cleavage
of APP or C99 was enhanced upon H2O2 treatment, expression of APP or
its alpha-/beta-secretase-mediated cleavage was not affected.
Silencing of the stress-activated JNK by siRNA or the specific JNK
inhibitor SP600125 reduced H2O2-induced gamma-secretase-mediated
cleavage of APP. JNK activity was augmented in human brain tissues
from AD patients, and active JNK located surrounding the senile
plaques in the brain of AD model mouse. Our data suggest that
oxidative stress-activated JNK may contribute to senile plaques
expansion through the promotion of gamma-secretase-mediated APP
cleavage and Abeta production.
The Journal of biological chemistry [J Biol Chem]
--------------------------------------------------------------------------------
Who loves ya.
Tom
Jesus Was A Vegetarian!
* tinyurl . com /2r2nkh
Man Is A Herbivore!
* tinyurl . com /a3cc3
DEAD PEOPLE WALKING
* tinyurl . com /zk9fk
Re: Oxidative Stress-activated JNK
On Apr 26, 8:07 am, "ironjust...@aol . com " <ironjust...@aol . com > wrote:
JNK-dependent activation of gamma -secretase. <<
"inhibition of JNK signaling achieved through iron sequestration"
<<snip>>
Our results suggest modulation of iron metabolism as a potential
approach for
anti-inflammatory therapy.
<<snip>>
Cell. 2004 Nov 12;119(4):529-42. Related Articles, Links
Ferritin Heavy Chain Upregulation by NF-kappaB Inhibits TNFalpha-
Induced
Apoptosis by Suppressing Reactive Oxygen Species.
Pham CG, Bubici C, Zazzeroni F, Papa S, Jones J, Alvarez K,
Jayawardena S, De
Smaele E, Cong R, Beaumont C, Torti FM, Torti SV, Franzoso G.
The Ben May Institute for Cancer Research and The University of
Chicago, 924
East 57th Street, Chicago, IL 60637 USA.
During inflammation, NF-kappaB transcription factors
antagonize apoptosis induced by tumor necrosis factor (TNF)alpha.
This antiapoptotic activity of NF-kappaB involves suppressing the
accumulation of reactive oxygen species (ROS) and controlling
the activation of the c-Jun N-terminal kinase (JNK) cascade.
However, the mechanism(s) by which NF-kappaB inhibits ROS
accumulation is unclear.
We identify ferritin heavy chain (FHC)-the primary iron storage
factor-as an essential mediator of the antioxidant and protective
activities of NF-kappaB.
FHC is induced downstream of NF-kappaB and is required to prevent
sustained JNK activation and, thereby, apoptosis triggered by
TNFalpha.
FHC-mediated inhibition of JNK signaling depends on suppressing ROS
accumulation and is achieved through iron sequestration.
These findings establish a basis for the NF-kappaB-mediated control of
ROS induction and identify a mechanism by which NF-kappaB suppresses
proapoptotic JNK signaling.
Our results suggest modulation of FHC or, more broadly, of iron
metabolism as a
potential approach for anti-inflammatory therapy.
PMID: 15537542 [PubMed - in process]
--------------------------------------------------------------------------
Who loves ya.
Tom
Jesus Was A Vegetarian!
* tinyurl . com /2r2nkh
Man Is A Herbivore!
* tinyurl . com /a3cc3
DEAD PEOPLE WALKING
* tinyurl . com /zk9fk
> Hydrogen peroxide promotes Abeta production through JNK-dependent
> activation of gamma -secretase.
> Shen C, Chen Y, Liu H, Zhang K, Zhang T, Lin A, Jing N
> J Biol Chem 2008 Apr 23.
>
> Accumulation of senile plaques composed of amyloid beta-peptide
> (Abeta) is a pathological hallmark of Alzheimer's disease (AD), and
> Abeta is generated through the sequential cleavage of amyloid
> precursor protein (APP) by beta- and gamma-secretase. Although
> oxidative stress has been implicated in AD pathogenesis by inducing
> Abeta production, the underlying mechanism remains elusive. Here we
> show that the pro-oxidant hydrogen peroxide (H2O2) promotes Abeta
> production through c-Jun N-terminal kinase (JNK)-dependent activation
> of gamma-secretase. Treatment with H2O2 induced significant increase
> in the levels of intracellular and secreted Abeta in human
> neuroblastoma SH-SY5Y cells. While gamma-secretase-mediated cleavage
> of APP or C99 was enhanced upon H2O2 treatment, expression of APP or
> its alpha-/beta-secretase-mediated cleavage was not affected.
> Silencing of the stress-activated JNK by siRNA or the specific JNK
> inhibitor SP600125 reduced H2O2-induced gamma-secretase-mediated
> cleavage of APP. JNK activity was augmented in human brain tissues
> from AD patients, and active JNK located surrounding the senile
> plaques in the brain of AD model mouse. Our data suggest that
> oxidative stress-activated JNK may contribute to senile plaques
> expansion through the promotion of gamma-secretase-mediated APP
> cleavage and Abeta production.
>
> The Journal of biological chemistry [J Biol Chem]
> --------------------------------------------------------------------------=
------
>
> Who loves ya.
> Tom
>
> Jesus Was A Vegetarian! * tinyurl . com /2r2nkh
>
> Man Is A Herbivore! * tinyurl . com /a3cc3
>
> DEAD PEOPLE WALKING * tinyurl . com /zk9fk
On Apr 26, 8:07 am, "ironjust...@aol . com " <ironjust...@aol . com > wrote:
JNK-dependent activation of gamma -secretase. <<
"inhibition of JNK signaling achieved through iron sequestration"
<<snip>>
Our results suggest modulation of iron metabolism as a potential
approach for
anti-inflammatory therapy.
<<snip>>
Cell. 2004 Nov 12;119(4):529-42. Related Articles, Links
Ferritin Heavy Chain Upregulation by NF-kappaB Inhibits TNFalpha-
Induced
Apoptosis by Suppressing Reactive Oxygen Species.
Pham CG, Bubici C, Zazzeroni F, Papa S, Jones J, Alvarez K,
Jayawardena S, De
Smaele E, Cong R, Beaumont C, Torti FM, Torti SV, Franzoso G.
The Ben May Institute for Cancer Research and The University of
Chicago, 924
East 57th Street, Chicago, IL 60637 USA.
During inflammation, NF-kappaB transcription factors
antagonize apoptosis induced by tumor necrosis factor (TNF)alpha.
This antiapoptotic activity of NF-kappaB involves suppressing the
accumulation of reactive oxygen species (ROS) and controlling
the activation of the c-Jun N-terminal kinase (JNK) cascade.
However, the mechanism(s) by which NF-kappaB inhibits ROS
accumulation is unclear.
We identify ferritin heavy chain (FHC)-the primary iron storage
factor-as an essential mediator of the antioxidant and protective
activities of NF-kappaB.
FHC is induced downstream of NF-kappaB and is required to prevent
sustained JNK activation and, thereby, apoptosis triggered by
TNFalpha.
FHC-mediated inhibition of JNK signaling depends on suppressing ROS
accumulation and is achieved through iron sequestration.
These findings establish a basis for the NF-kappaB-mediated control of
ROS induction and identify a mechanism by which NF-kappaB suppresses
proapoptotic JNK signaling.
Our results suggest modulation of FHC or, more broadly, of iron
metabolism as a
potential approach for anti-inflammatory therapy.
PMID: 15537542 [PubMed - in process]
--------------------------------------------------------------------------
Who loves ya.
Tom
Jesus Was A Vegetarian!
* tinyurl . com /2r2nkh
Man Is A Herbivore!
* tinyurl . com /a3cc3
DEAD PEOPLE WALKING
* tinyurl . com /zk9fk
> Hydrogen peroxide promotes Abeta production through JNK-dependent
> activation of gamma -secretase.
> Shen C, Chen Y, Liu H, Zhang K, Zhang T, Lin A, Jing N
> J Biol Chem 2008 Apr 23.
>
> Accumulation of senile plaques composed of amyloid beta-peptide
> (Abeta) is a pathological hallmark of Alzheimer's disease (AD), and
> Abeta is generated through the sequential cleavage of amyloid
> precursor protein (APP) by beta- and gamma-secretase. Although
> oxidative stress has been implicated in AD pathogenesis by inducing
> Abeta production, the underlying mechanism remains elusive. Here we
> show that the pro-oxidant hydrogen peroxide (H2O2) promotes Abeta
> production through c-Jun N-terminal kinase (JNK)-dependent activation
> of gamma-secretase. Treatment with H2O2 induced significant increase
> in the levels of intracellular and secreted Abeta in human
> neuroblastoma SH-SY5Y cells. While gamma-secretase-mediated cleavage
> of APP or C99 was enhanced upon H2O2 treatment, expression of APP or
> its alpha-/beta-secretase-mediated cleavage was not affected.
> Silencing of the stress-activated JNK by siRNA or the specific JNK
> inhibitor SP600125 reduced H2O2-induced gamma-secretase-mediated
> cleavage of APP. JNK activity was augmented in human brain tissues
> from AD patients, and active JNK located surrounding the senile
> plaques in the brain of AD model mouse. Our data suggest that
> oxidative stress-activated JNK may contribute to senile plaques
> expansion through the promotion of gamma-secretase-mediated APP
> cleavage and Abeta production.
>
> The Journal of biological chemistry [J Biol Chem]
> --------------------------------------------------------------------------=
------
>
> Who loves ya.
> Tom
>
> Jesus Was A Vegetarian! * tinyurl . com /2r2nkh
>
> Man Is A Herbivore! * tinyurl . com /a3cc3
>
> DEAD PEOPLE WALKING * tinyurl . com /zk9fk
