Science and Technology news... :: View topic - The "good" face of arachidonic acid

Taka · Guest

In addition to the previously discussed stimulation of TREGs by PGE2
(Kofi) here is a new study showing that PGE2 downregulates TNF-alpha
(the papers by Marnett LJ are generally interesting in respect to
lipid peroxide-induced damage):

Biochem Biophys Res Commun. 2008 Feb 1;366(1):104-9. Epub 2007 Dec 3.

Prostaglandin E2 inhibits tumor necrosis factor-alpha RNA through PKA
type I.

Stafford JB, Marnett LJ.
Department of Biochemistry, Vanderbilt University School of Medicine,
23rd Avenue South at Pierce, Nashville, TN 37232-0146, USA.

Tumor necrosis factor-alpha (TNF-alpha) is a cytokine that may
contribute to the pathogenesis of septic shock, rheumatoid arthritis,
cancer, and diabetes. Prostaglandins endogenously produced by
macrophages act in an autocrine fashion to limit TNF-alpha production.
We investigated the timing and signaling pathway of prostaglandin-
mediated inhibition of TNF-alpha production in Raw 264.7 and J774
macrophages. TNF-alpha mRNA levels were rapidly modulated by PGE(2) or
carbaprostacylin. PGE(2) or carbaprostacyclin prevented and rapidly
terminated on-going TNF-alpha gene transcription within 15 min of
prostaglandin treatment. Selective activation of PKA type I, but not
PKA type II or Epac, with chemical analogs of cAMP was sufficient to
inhibit LPS-induced TNF-alpha mRNA levels. The mechanisms by which
prostaglandins limit TNF-alpha mRNA levels may underlie endogenous
regulatory mechanisms that limit inflammation, and may have important
implications for understanding chronic inflammatory disease
pathogenesis.
PMID: 18060853

Taka · Guest

But the price paid for the benefits of PGE2 may be too high especially
in the long term. During PGE2 biosynthesis the bad MDA side-product
is also produced:

Toxicology. 2002 Dec 27;181-182:219-22.

Oxy radicals, lipid peroxidation and DNA damage.

Marnett LJ.
A.B. Hancock Jr. Memorial Laboratory for Cancer Research, Center in
Molecular Toxicology and the Vanderbilt Cancer Center, Department of
Biochemistry, Vanderbilt University School of Medicine, Nashville, TN
37232, USA.

Oxygen radicals react with polyunsaturated fatty acid residues in
phospholipids resulting in the production of a plethora of products,
many of them reactive toward protein and DNA. One of the most abundant
carbonyl products of lipid peroxidation is malondialdehyde (MDA),
which also is generated as a side-product of prostaglandin
biosynthesis. It reacts with DNA to form adducts to deoxyguanosine,
deoxyadenosine, and deoxycytidine. The deoxyguanosine adduct (M(1)G)
has been detected in liver, white blood cells, colon, pancreas, and
breast from healthy human beings at levels ranging from 1 to 120 per
10(8) nucleotides. Random and site-specific mutagenesis experiments
indicate that MDA-DNA adducts are mutagenic in bacteria and in
mammalian cells. M(1)G is highly mutagenic when incorporated into
viral genomes then replicated in E. coli. It is repaired by the
nucleotide excision repair pathway. Lipid peroxidation appears to be a
major source of endogenous DNA damage in humans that may contribute
significantly to cancer and other genetic diseases linked to lifestyle
and dietary factors.
PMID: 12505314

Guest

If PGE2 was essential, I>d be dead now. If it was optimal, my health
would have deteriorated on a diet that leads to AA replacement by Mead
acid (and so now my body doesn>t produce PGE2). Instead, when I
switched over to the anti-AA diet, I was in terrible shape physically,
with severe osteoporosis, wasting away (less than 100 pounds as a 5>9"
tall male), horrible rosacea, fatigue, frequent infections, etc., so
if this switch was even slight unhealthy I>d have killed myself.
Instead, I "cured" myself on this diet, and now weigh in the 130s with
no rosacea, no osteoporosis, etc.

jay · Guest

[quote]was in terrible shape physically, with severe osteoporosis,
wasting away, horrible rosacea, fatigue, frequent infections, etc.
[/quote]
Does your osteoporosis include erosion of dental enamel?
Do citrus, cruciferous veggie or spices affect you?

Guest

I think what they called osteoporosis had begun long before. When I
was about 20, I switched over to a vegan diet and lost quite a bit of
weight, going down to less than 120 pounds. By my mid 30s, I was in
the low 130s, and I think this was due to some sort of chronic
inflammatory issue (I looked a lit bloated at the time, compared to
now). Most likely this was due to what biologist Ray Peat calls the
loss of the "youth associated hormones." I was also on a no
cholesterol diet, since it was vegan. Cholesterol is important, and
my cholesterol was very low at the time (though at least I wasn>t
eating oxidized cholesterol). Then, with a very low salt diet, I
stopped producing stomach acid, and of course the doctors didn>t
understand what the problem was, and the wasting began. After adding
animal protein (mostly cheese with some boiled eggs), stomach acid
supplements, and calcium citrate, I began to gain weight, and
eventually got to where I am now, mid 130s.

I did have to have two decayed teeth pulled but otherwise there
doesn>t seem to have been a major dental issue. However, I>ve been
very rigorous in teeth cleaning for a long time, doing my own de-
scaling, or whatever they call it, on a daily basis.

I don>t seem to have problems with those items you mentioned, but I
only eat small amounts of things that are hard to digest. I don>t eat
much of any of them any more, so perhaps if I ate larger amounts any
or all of them could be problematic. I do make a hot chili dip once
in a while, and that>s not a problem, though again I don>t use much of
it.

Marshall Price · Guest

monty1945@lycos.com wrote:
[quote]If PGE2 was essential, I>d be dead now. If it was optimal, my health
would have deteriorated on a diet that leads to AA replacement by Mead
acid (and so now my body doesn>t produce PGE2). Instead, when I
switched over to the anti-AA diet, I was in terrible shape physically,
with severe osteoporosis, wasting away (less than 100 pounds as a 5>9"
tall male), horrible rosacea, fatigue, frequent infections, etc., so
if this switch was even slight unhealthy I>d have killed myself.
Instead, I "cured" myself on this diet, and now weigh in the 130s with
no rosacea, no osteoporosis, etc.
[/quote]
Can you explain the diet briefly?

--
Marshall Price of Miami
Known to Yahoo as d021317c


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