Similar in structure and effects to sugar ...

Taka

Mol Cell Biochem. 2008 May 22.

Redox-active antioxidant modulation of lipid signaling in vascular
endothelial cells: vitamin C induces activation of phospholipase D
through phospholipase A(2), lipoxygenase, and cyclooxygenase.

Steinhour E, Sherwani SI, Mazerik JN, Ciapala V, O'Connor Butler E,
Cruff JP, Magalang U, Parthasarathy S, Sen CK, Marsh CB, Kuppusamy P,
Parinandi NL.
Lipid Signaling and Lipidomics Laboratory, Division of Pulmonary,
Allergy, Critical Care, and Sleep Medicine, Department of Medicine,
College of Medicine, The Ohio State University, Columbus, OH, USA.

We have earlier reported that the redox-active antioxidant, vitamin C
(ascorbic acid), activates the lipid signaling enzyme, phospholipase D
(PLD), at pharmacological doses (mM) in the bovine lung microvascular
endothelial cells (BLMVECs). However, the activation of phospholipase
A(2) (PLA(2)), another signaling phospholipase, and the modulation of
PLD activation by PLA(2) in the ECs treated with vitamin C at
pharmacological doses have not been reported to date. Therefore, this
study aimed at the regulation of PLD activation by PLA(2) in the
cultured BLMVECs exposed to vitamin C at pharmacological
concentrations. The results revealed that vitamin C (3-10 mM)
significantly activated PLA(2) starting at 30 min; however, the
activation of PLD resulted only at 120 min of treatment of cells under
identical conditions. Further studies were conducted utilizing
specific pharmacological agents to understand the mechanism(s) of
activation of PLA(2) and PLD in BLMVECs treated with vitamin C (5 mM)
for 120 min. Antioxidants, calcium chelators, iron chelators, and
PLA(2) inhibitors offered attenuation of the vitamin C-induced
activation of both PLA(2) and PLD in the cells. Vitamin C was also
observed to significantly induce the formation and release of the
cyclooxygenase (COX)- and lipoxygenase (LOX)-catalyzed arachidonic
acid (AA) metabolites and to activate the AA LOX in BLMVECs. The
inhibitors of PLA(2), COX, and LOX were observed to effectively and
significantly attenuate the vitamin C-induced PLD activation in
BLMVECs. For the first time, the results of the present study revealed
that the vitamin C-induced activation of PLD in vascular ECs was
regulated by the upstream activation of PLA(2), COX, and LOX through
the formation of AA metabolites involving oxidative stress, calcium,
and iron.
PMID: 18496733

Similar in structure and effects to sugar ...
Taka

Mol Cell Biochem. 2008 May 22.

Redox-active antioxidant modulation of lipid signaling in vascular
endothelial cells: vitamin C induces activation of phospholipase D
through phospholipase A(2), lipoxygenase, and cyclooxygenase.

Steinhour E, Sherwani SI, Mazerik JN, Ciapala V, O'Connor Butler E,
Cruff JP, Magalang U, Parthasarathy S, Sen CK, Marsh CB, Kuppusamy P,
Parinandi NL.
Lipid Signaling and Lipidomics Laboratory, Division of Pulmonary,
Allergy, Critical Care, and Sleep Medicine, Department of Medicine,
College of Medicine, The Ohio State University, Columbus, OH, USA.

We have earlier reported that the redox-active antioxidant, vitamin C
(ascorbic acid), activates the lipid signaling enzyme, phospholipase D
(PLD), at pharmacological doses (mM) in the bovine lung microvascular
endothelial cells (BLMVECs). However, the activation of phospholipase
A(2) (PLA(2)), another signaling phospholipase, and the modulation of
PLD activation by PLA(2) in the ECs treated with vitamin C at
pharmacological doses have not been reported to date. Therefore, this
study aimed at the regulation of PLD activation by PLA(2) in the
cultured BLMVECs exposed to vitamin C at pharmacological
concentrations. The results revealed that vitamin C (3-10 mM)
significantly activated PLA(2) starting at 30 min; however, the
activation of PLD resulted only at 120 min of treatment of cells under
identical conditions. Further studies were conducted utilizing
specific pharmacological agents to understand the mechanism(s) of
activation of PLA(2) and PLD in BLMVECs treated with vitamin C (5 mM)
for 120 min. Antioxidants, calcium chelators, iron chelators, and
PLA(2) inhibitors offered attenuation of the vitamin C-induced
activation of both PLA(2) and PLD in the cells. Vitamin C was also
observed to significantly induce the formation and release of the
cyclooxygenase (COX)- and lipoxygenase (LOX)-catalyzed arachidonic
acid (AA) metabolites and to activate the AA LOX in BLMVECs. The
inhibitors of PLA(2), COX, and LOX were observed to effectively and
significantly attenuate the vitamin C-induced PLD activation in
BLMVECs. For the first time, the results of the present study revealed
that the vitamin C-induced activation of PLD in vascular ECs was
regulated by the upstream activation of PLA(2), COX, and LOX through
the formation of AA metabolites involving oxidative stress, calcium,
and iron.
PMID: 18496733

Surely you realize this stuff is hard reading or incomprehensible to
almost everybody in this newsgroup but you, so please help us understand
what it says and why you said what you did.

Taka wrote:
Similar in structure and effects to sugar ...
Taka

Mol Cell Biochem. 2008 May 22.

Redox-active antioxidant modulation of lipid signaling in vascular
endothelial cells: vitamin C induces activation of phospholipase D
through phospholipase A(2), lipoxygenase, and cyclooxygenase.

Come on, Taka. You chose the subject line, and you said "similar in
structure and effects to sugar," and this is a discussion group, so how
about some discussion?

On Jun 12, 8:10 pm, Marshall Price <d0213... at (no spam) yahoo.com> wrote:

Taka wrote:
Similar in structure and effects to sugar ...
Taka

Mol Cell Biochem. 2008 May 22.

Redox-active antioxidant modulation of lipid signaling in vascular
endothelial cells: vitamin C induces activation of phospholipase D
through phospholipase A(2), lipoxygenase, and cyclooxygenase.
Come on, Taka. You chose the subject line, and you said "similar in
structure and effects to sugar," and this is a discussion group, so how
about some discussion?

Just another inflammatory (hoho) and disingenous headline from Taka,
I'm afraid.

Having looked briefly at the paper the whole thing is very non-
specific. Basically when you raise blood levels of vitamin C to
*pharmacological* levels by directly injecting Vit C into the
bloodstream (i.e. not by eating supplements) you see increased
activation of molecules involved in oxidative stress.

In the presence of iron, vitamin C can become a free radical that can
then damage other molecules and lead to activation of various enzymes.
One of these causes the release of arachidonic acid within the cell.
These is as specific as the connection is.

Mentioning sugar is a
complete red herring.

Any molecule that can become a free radical
through interaction with iron will have the same effect.

On Jun 12, 8:10 pm, Marshall Price <d0213... at (no spam) yahoo.com> wrote:
Taka wrote:
Similar in structure and effects to sugar ...
Taka

Mol Cell Biochem. 2008 May 22.

Redox-active antioxidant modulation of lipid signaling in vascular
endothelial cells: vitamin C induces activation of phospholipase D
through phospholipase A(2), lipoxygenase, and cyclooxygenase.

Come on, Taka. You chose the subject line, and you said "similar in
structure and effects to sugar," and this is a discussion group, so how
about some discussion?

Just another inflammatory (hoho) and disingenous headline from Taka,
I'm afraid.

Having looked briefly at the paper the whole thing is very non-
specific. Basically when you raise blood levels of vitamin C to
*pharmacological* levels by directly injecting Vit C into the
bloodstream (i.e. not by eating supplements) you see increased
activation of molecules involved in oxidative stress.

In the presence of iron, vitamin C can become a free radical that can
then damage other molecules and lead to activation of various enzymes.

One of these causes the release of arachidonic acid within the cell.
These is as specific as the connection is. Mentioning sugar is a
complete red herring. Any molecule that can become a free radical
through interaction with iron will have the same effect.

The experiments were also done using cells growing in flasks, with
vitamin C directly added to the cell medium, so have rather little
connection to the human body where the vitamin C is consumed along
with a host of other molecules.

MattLB

On Jun 13, 9:33 pm, MattLB <mat... at (no spam) angelfire.com> wrote:
On Jun 12, 8:10 pm, Marshall Price <d0213... at (no spam) yahoo.com> wrote:

Taka wrote:
Similar in structure and effects to sugar ...
Taka

Mol Cell Biochem. 2008 May 22.

Redox-active antioxidant modulation of lipid signaling in vascular
endothelial cells: vitamin C induces activation of phospholipase D
through phospholipase A(2), lipoxygenase, and cyclooxygenase.
Come on, Taka. You chose the subject line, and you said "similar in
structure and effects to sugar," and this is a discussion group, so how
about some discussion?

Just another inflammatory (hoho) and disingenous headline from Taka,
I'm afraid.

Having looked briefly at the paper the whole thing is very non-
specific. Basically when you raise blood levels of vitamin C to
*pharmacological* levels by directly injecting Vit C into the
bloodstream (i.e. not by eating supplements) you see increased
activation of molecules involved in oxidative stress.

In the presence of iron, vitamin C can become a free radical that can
then damage other molecules and lead to activation of various enzymes.
One of these causes the release of arachidonic acid within the cell.
These is as specific as the connection is.

And as specific as the chronic inflammatory states are ...

Mentioning sugar is a
complete red herring.

Yet VitC is made from sugar, enters cells via the same receptors as
sugar and its absorption is competitively inhibited by sugar ...

Any molecule that can become a free radical
through interaction with iron will have the same effect.

Like our wonderful PUFAs. BTW you forgot oxygen without which iron is
powerless. The combination O2+Fe+VitC+PUFAs is the best setting for
getting full spectrum of lipid hydroperoxides and free radicals and
you can even get so called AGEs if you throw in sugars.

I have mentioned previously how sugar and saturated fatty acids (which
are rare in their free form in the body BTW) release AA:

http://tinyurl.com/52y4kk

http://tinyurl.com/4c6w9l

And a recent article has been posted showing how the carbohydrate
restriction has antiinflammatory effects even in people full of AA:

Lipids. 2008 Jan;43(1):65-77. Epub 2007 Nov 29.

Comparison of low fat and low carbohydrate diets on circulating fatty
acid composition and markers of inflammation.

Forsythe CE, Phinney SD, Fernandez ML, Quann EE, Wood RJ, Bibus DM,
Kraemer WJ, Feinman RD, Volek JS.
Department of Kinesiology, University of Connecticut, 2095 Hillside
Road, Unit 1110, Storrs, CT, 06269-1110, USA.

Abnormal distribution of plasma fatty acids and increased inflammation
are prominent features of metabolic syndrome. We tested whether these
components of metabolic syndrome, like dyslipidemia and glycemia, are
responsive to carbohydrate restriction. Overweight men and women with
atherogenic dyslipidemia consumed ad libitum diets very low in
carbohydrate (VLCKD) (1504 kcal:%CHO:fat:protein = 12:59:2 or low in
fat (LFD) (1478 kcal:%CHO:fat:protein = 56:24:20) for 12 weeks. In
comparison to the LFD, the VLCKD resulted in an increased proportion
of serum total n-6 PUFA, mainly attributed to a marked increase in
arachidonate (20:4n-6), while its biosynthetic metabolic intermediates
were decreased. The n-6/n-3 and arachidonic/eicosapentaenoic acid
ratio also increased sharply. Total saturated fatty acids and 16:1n-7
were consistently decreased following the VLCKD. Both diets
significantly decreased the concentration of several serum
inflammatory markers, but there was an overall greater anti-
inflammatory effect associated with the VLCKD, as evidenced by greater
decreases in TNF-alpha, IL-6, IL-8, MCP-1, E-selectin, I-CAM, and
PAI-1. Increased 20:4n-6 and the ratios of 20:4n-6/20:5n-3 and n-6/n-3
are commonly viewed as pro-inflammatory, but unexpectedly were
consistently inversely associated with responses in inflammatory
proteins. In summary, a very low carbohydrate diet resulted in
profound alterations in fatty acid composition and reduced
inflammation compared to a low fat diet.
PMID: 18046594

Taka

Highly unlikely, as per my response to MattLB.
VitC (fresh Vit C, at any rate) is a reducing agent, likely rendering O2, Fe
etc. unable to oxidize pufa's. It is a kind of sacrificial molecule,

Taka wrote:
Similar in structure and effects to sugar ...
Taka

Mol Cell Biochem. 2008 May 22.

Redox-active antioxidant modulation of lipid signaling in vascular
endothelial cells: vitamin C induces activation of phospholipase D
through phospholipase A(2), lipoxygenase, and cyclooxygenase.

Steinhour E, Sherwani SI, Mazerik JN, Ciapala V, O'Connor Butler E,
Cruff JP, Magalang U, Parthasarathy S, Sen CK, Marsh CB, Kuppusamy P,
Parinandi NL.
Lipid Signaling and Lipidomics Laboratory, Division of Pulmonary,
Allergy, Critical Care, and Sleep Medicine, Department of Medicine,
College of Medicine, The Ohio State University, Columbus, OH, USA.

We have earlier reported that the redox-active antioxidant, vitamin C
(ascorbic acid), activates the lipid signaling enzyme, phospholipase D
(PLD), at pharmacological doses (mM) in the bovine lung microvascular
endothelial cells (BLMVECs). However, the activation of phospholipase
A(2) (PLA(2)), another signaling phospholipase, and the modulation of
PLD activation by PLA(2) in the ECs treated with vitamin C at
pharmacological doses have not been reported to date. Therefore, this
study aimed at the regulation of PLD activation by PLA(2) in the
cultured BLMVECs exposed to vitamin C at pharmacological
concentrations. The results revealed that vitamin C (3-10 mM)
significantly activated PLA(2) starting at 30 min; however, the
activation of PLD resulted only at 120 min of treatment of cells under
identical conditions. Further studies were conducted utilizing
specific pharmacological agents to understand the mechanism(s) of
activation of PLA(2) and PLD in BLMVECs treated with vitamin C (5 mM)
for 120 min. Antioxidants, calcium chelators, iron chelators, and
PLA(2) inhibitors offered attenuation of the vitamin C-induced
activation of both PLA(2) and PLD in the cells. Vitamin C was also
observed to significantly induce the formation and release of the
cyclooxygenase (COX)- and lipoxygenase (LOX)-catalyzed arachidonic
acid (AA) metabolites and to activate the AA LOX in BLMVECs. The
inhibitors of PLA(2), COX, and LOX were observed to effectively and
significantly attenuate the vitamin C-induced PLD activation in
BLMVECs. For the first time, the results of the present study revealed
that the vitamin C-induced activation of PLD in vascular ECs was
regulated by the upstream activation of PLA(2), COX, and LOX through
the formation of AA metabolites involving oxidative stress, calcium,
and iron.
PMID: 18496733

Come on, Taka. You chose the subject line, and you said "similar in
structure and effects to sugar," and this is a discussion group, so how
about some discussion?

Sugar has 12 carbons; ascorbic acid has six. Sugar provides quick
energy, ascorbic acid provides none. Most antioxidants are
anti-inflammatory; ascorbic acid is an antioxidant, but you say it's
"proinflammatory."

Surely you realize this stuff is hard reading or incomprehensible to
almost everybody in this newsgroup but you, so please help us understand
what it says and why you said what you did.

--
Marshall Price of Miami
Known to Yahoo as d021317c

In the context of a large free iron pool(and possibly other metals)
vitamin C might be pro-inflammatory. Otherwise ... Don't sweat PLA2 so
much, it is even released via glutamate activity, as is AA. Both help.
Balance, concentrations, context, not presence or absence.

"Marshall Price" <d021317c at (no spam) yahoo.com> wrote in message
news:raqdnWzghfEv6czVnZ2dnUVZ_oTinZ2d at (no spam) earthlink.com...
Taka wrote:
Similar in structure and effects to sugar ...
Taka

Mol Cell Biochem. 2008 May 22.

Redox-active antioxidant modulation of lipid signaling in vascular
endothelial cells: vitamin C induces activation of phospholipase D
through phospholipase A(2), lipoxygenase, and cyclooxygenase.

Steinhour E, Sherwani SI, Mazerik JN, Ciapala V, O'Connor Butler E,
Cruff JP, Magalang U, Parthasarathy S, Sen CK, Marsh CB, Kuppusamy P,
Parinandi NL.
Lipid Signaling and Lipidomics Laboratory, Division of Pulmonary,
Allergy, Critical Care, and Sleep Medicine, Department of Medicine,
College of Medicine, The Ohio State University, Columbus, OH, USA.

We have earlier reported that the redox-active antioxidant, vitamin C
(ascorbic acid), activates the lipid signaling enzyme, phospholipase D
(PLD), at pharmacological doses (mM) in the bovine lung microvascular
endothelial cells (BLMVECs). However, the activation of phospholipase
A(2) (PLA(2)), another signaling phospholipase, and the modulation of
PLD activation by PLA(2) in the ECs treated with vitamin C at
pharmacological doses have not been reported to date. Therefore, this
study aimed at the regulation of PLD activation by PLA(2) in the
cultured BLMVECs exposed to vitamin C at pharmacological
concentrations. The results revealed that vitamin C (3-10 mM)
significantly activated PLA(2) starting at 30 min; however, the
activation of PLD resulted only at 120 min of treatment of cells under
identical conditions. Further studies were conducted utilizing
specific pharmacological agents to understand the mechanism(s) of
activation of PLA(2) and PLD in BLMVECs treated with vitamin C (5 mM)
for 120 min. Antioxidants, calcium chelators, iron chelators, and
PLA(2) inhibitors offered attenuation of the vitamin C-induced
activation of both PLA(2) and PLD in the cells. Vitamin C was also
observed to significantly induce the formation and release of the
cyclooxygenase (COX)- and lipoxygenase (LOX)-catalyzed arachidonic
acid (AA) metabolites and to activate the AA LOX in BLMVECs. The
inhibitors of PLA(2), COX, and LOX were observed to effectively and
significantly attenuate the vitamin C-induced PLD activation in
BLMVECs. For the first time, the results of the present study revealed
that the vitamin C-induced activation of PLD in vascular ECs was
regulated by the upstream activation of PLA(2), COX, and LOX through
the formation of AA metabolites involving oxidative stress, calcium,
and iron.
PMID: 18496733

Come on, Taka. You chose the subject line, and you said "similar in
structure and effects to sugar," and this is a discussion group, so how
about some discussion?

Sugar has 12 carbons; ascorbic acid has six. Sugar provides quick
energy, ascorbic acid provides none. Most antioxidants are
anti-inflammatory; ascorbic acid is an antioxidant, but you say it's
"proinflammatory."

Surely you realize this stuff is hard reading or incomprehensible to
almost everybody in this newsgroup but you, so please help us understand
what it says and why you said what you did.

--
Marshall Price of Miami
Known to Yahoo as d021317c

Small/appropriate VitC amount at the right place is good and essential
for e.g. collagen synthesis. Large amount at the wrong place may be
dangerous depending on the presence of Fe, PUFAs and the like. AFAIK
there are fewer studies, if any, showing a proinflammatory properties
of VitE. VitE protects from lipid peroxides while VitC may facilitate
their formation. Since lipid peroxides are proapoptotic and activate
p53 high doses of VitC are used intravenously to kill cancers. The
genotoxicity of VitC was refuted later by an artificial system in
vitro experiment which I wouldn't trust as much as the original
Science paper:

Science 15 June 2001:
Vol. 292. no. 5524, pp. 2083 - 2086
DOI: 10.1126/science.1059501

Vitamin C-Induced Decomposition of Lipid Hydroperoxides to Endogenous
Genotoxins

Seon Hwa Lee, Tomoyuki Oe, Ian A. Blair*

Epidemiological data suggest that dietary antioxidants play a
protective role against cancer. This has led to the proposal that
dietary supplementation with antioxidants such as vitamin C (vit C)
may be useful in disease prevention. However, vit C has proved to be
ineffective in cancer chemoprevention studies. In addition, concerns
have been raised over potentially deleterious transition metal ion-
mediated pro-oxidant effects. We have now determined that vit C
induces lipid hydroperoxide decomposition to the DNA-reactive
bifunctional electrophiles 4-oxo-2-nonenal, 4,5-epoxy-2(E)-decenal,
and 4-hydroxy-2-nonenal. The compound 4,5-Epoxy-2(E)-decenal is a
precursor of etheno-2'-deoxyadenosine, a highly mutagenic lesion
found
in human DNA. Vitamin C-mediated formation of genotoxins from lipid
hydroperoxides in the absence of transition metal ions could help
explain its lack of efficacy as a cancer chemoprevention agent.

For you "Boy Scout chemists", do you have any idea what the transition
metal ion-
mediated pro-oxidant effects are? This is different from the PLA2
induction

Taka

Small/appropriate VitC amount at the right place is good and essential
for e.g. collagen synthesis. Large amount at the wrong place may be
dangerous depending on the presence of Fe, PUFAs and the like. AFAIK
there are fewer studies, if any, showing a proinflammatory properties
of VitE. VitE protects from lipid peroxides while VitC may facilitate
their formation. Since lipid peroxides are proapoptotic and activate
p53 high doses of VitC are used intravenously to kill cancers. The
genotoxicity of VitC was refuted later by an artificial system in
vitro experiment which I wouldn't trust as much as the original
Science paper:

Science 15 June 2001:
Vol. 292. no. 5524, pp. 2083 - 2086
DOI: 10.1126/science.1059501

Vitamin C-Induced Decomposition of Lipid Hydroperoxides to Endogenous
Genotoxins

Seon Hwa Lee, Tomoyuki Oe, Ian A. Blair*

Epidemiological data suggest that dietary antioxidants play a
protective role against cancer. This has led to the proposal that
dietary supplementation with antioxidants such as vitamin C (vit C)
may be useful in disease prevention. However, vit C has proved to be
ineffective in cancer chemoprevention studies. In addition, concerns
have been raised over potentially deleterious transition metal ion-
mediated pro-oxidant effects. We have now determined that vit C
induces lipid hydroperoxide decomposition to the DNA-reactive
bifunctional electrophiles 4-oxo-2-nonenal, 4,5-epoxy-2(E)-decenal,
and 4-hydroxy-2-nonenal. The compound 4,5-Epoxy-2(E)-decenal is a
precursor of etheno-2'-deoxyadenosine, a highly mutagenic lesion
found
in human DNA. Vitamin C-mediated formation of genotoxins from lipid
hydroperoxides in the absence of transition metal ions could help
explain its lack of efficacy as a cancer chemoprevention agent.

For you "Boy Scout chemists", do you have any idea what the transition
metal ion-
mediated pro-oxidant effects are? This is different from the PLA2
induction

Taka

On Jun 13, 9:33 pm, MattLB <mat... at (no spam) angelfire.com> wrote:

Mentioning sugar is a
complete red herring.

Yet VitC is made from sugar,

enters cells via the same receptors as
sugar and its absorption is competitively inhibited by sugar ...

Any molecule that can become a free radical
through interaction with iron will have the same effect.

Like our wonderful PUFAs. BTW you forgot oxygen without which iron is
powerless.

The combination O2+Fe+VitC+PUFAs is the best setting for
getting full spectrum of lipid hydroperoxides and free radicals and
you can even get so called AGEs if you throw in sugars.

I have mentioned previously how sugar and saturated fatty acids (which
are rare in their free form in the body BTW)