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Does dht effect proteolytic systems

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mike

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Nov 29, 2001, 3:41:49 AM11/29/01
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http://www.lef.org/magazine/mag2001/jan2001_report_carnosine2_1.html

Carnosine's effects on proteolysis:

snip...

Timely proteolysis removes damaged proteins before they do significant
harm, and removes undamaged proteins before they become damaged or
disruptive. For example, if oxidized proteins are not broken down, they
tend to cross-link and aggregate (as, for example, in cataracts or senile
plaques). Rapid effective proteolysis is therefore an anti-aging mechanism
(Grune T et al., 1997).

The main proteolytic enzyme complex is called the proteasome. It removes
proteins that have been tagged for degradation by a peptide called
ubiquitin. Through its role in protein disposal, the proteasome-ubiquitin
pathway helps regulate many basic cellular processes including the cell
cycle and cell division, cell differentiation, cellular signaling,
cellular metabolism and DNA repair (Ciechanover A, 1998). Thus a
malfunctioning proteasomal system has far-reaching consequences.

As cells age, after many cell divisions, proteasome activity declines
(Sitte N et al., 2000; Merker K et al., 2000). At the same time, more and
more proteins undergo damage through a process called carbonylation. Thus
the proteolytic system becomes increasingly inadequate to deal with the
increasing numbers of abnormal or unneeded proteins, which can
irreversibly form cross-links and turn cellular processes awry.

New research shows that when the population of carbonylated proteins
permanently increases—as in aging—proteasome activity is depressed
(Petropoulos I et al., 2000; Keller JN et al., 2000; Burcham PC et al.,
1997). A vicious circle develops of age-related decline in proteasomal
activity, age-related increase in protein carbonylation and further
inhibition of the proteasome. The life cycles of proteins become blocked,
and the normal turnover of protein declines.

Is there a way to block this vicious circle? The body contains a dipeptide
called carnosine that both protects proteins from carbonylation and helps
reverse proteasomal decline. As in the aging body, proteolysis declines in
cultured cells as they approach senescence. Australian scientists showed
that carnosine enhances intracellular proteolytic activity in human
connective tissue cells (Hipkiss AR et al., 1995). Carnosine enhanced
proteolysis the most in old cells, and to a lesser extent in “middle aged”
cells, compensating for age-related proteolytic decline (for details see
“Carnosine—Nature's pluripotent life extension agent” from this issue).

""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""
Does dht do something to serine proteases to disrupt damaged cell
proteins? Enuff damaged cell proteins = shutdown(senescence)

: J Invest Dermatol 1999 Sep;113(3):308-13 Related Articles, Books,
LinkOut


The mRNA for protease nexin-1 is expressed in human dermal papilla cells
and its level is affected by androgen.

Sonoda T, Asada Y, Kurata S, Takayasu S.

Department of Dermatology, Oita Medical University, Hasama, Japan.
son...@oita-med.ac.jp

Protease nexin-1, an inhibitor of serine proteases, plays important parts
in the regulation of the growth, differentiation, and death of cells by
modulating proteolytic activity. The mRNA for protease nexin-1 accumulates
in rat dermal papilla cells in a hair cycle-dependent fashion and its
levels are well correlated with the ability of dermal papilla cells to
support hair growth. In an attempt to characterize the potential role of
protease nexin-1 as a modulator of hair growth in humans, we investigated
the steady-state level of protease nexin-1 mRNA in cultured human dermal
papilla cells using a semiquantitative technique that involved reverse
transcription and polymerase chain reaction, as well as the localization
of this mRNA in vivo using dissected hair follicles. Protease nexin-1 mRNA
was expressed in all dermal papilla cells examined, and it was also
identified in the lower part of the connective tissue sheath. Moreover, we
found that levels of protease nexin-1 mRNA were depressed by
dihydrotestosterone, the most potent androgen, in cultured dermal papilla
cells obtained from balding scalp. Our results suggest that protease
nexin-1 might be a key molecule in the control of hair growth in humans
and, moreover, that the androgen-mediated downregulation of the synthesis
of protease nexin-1 might be associated with the progression of
male-pattern baldness.

PMID: 10469326 [PubMed - indexed for MEDLINE]

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mike

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Nov 29, 2001, 3:43:36 AM11/29/01
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Man oh man..this is gotta be close!

mike

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Nov 29, 2001, 5:02:48 AM11/29/01
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Further,from page 2:
http://www.lef.org/magazine/mag2001/jan2001_report_carnosine2_2.html

snip...
Proteolysis of connective tissue is a normal part of skin cell development
and wound healing. Proteolytic enzymes and their inhibitors sculpt
structural proteins and break them down at the appropriate times.
Unfortunately, as aging skin cells senesce and *increase their proteolytic
activity*, the proteasome (the main enzyme complex for protein
degradation) enters an age-related decline. The balance between protein
creation and destruction is again upset, compromising the integrity and
regeneration of skin tissue.


Nuclear

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Nov 24, 2001, 11:38:59 PM11/24/01
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Mike, a while ago I postulated using the proteolytic enzyme serrapeptase on
the scalp to get rid of the stuff constricting the follicle. You wrote back
to me and said to be wary of using proteolytic enzymes on your scalp. Are
you know changing your mind based on further research? Is it now feasible to
use proteolytic enzymes like serrapeptase on your scalp and if it is can I
just crush the pills and mix them in water and apply it? Will the enzyme
still be "alive", I believe enzymes are tricky things to control.

Thanks.

"mike" <emka...@dodgenet.com> wrote in message
news:9u5148$vpb$1...@ins21.netins.net...

> >permanently increases-as in aging-proteasome activity is depressed


> >(Petropoulos I et al., 2000; Keller JN et al., 2000; Burcham PC et al.,
> >1997). A vicious circle develops of age-related decline in proteasomal
> >activity, age-related increase in protein carbonylation and further
> >inhibition of the proteasome. The life cycles of proteins become blocked,
> >and the normal turnover of protein declines.
> >
> >Is there a way to block this vicious circle? The body contains a
dipeptide
> >called carnosine that both protects proteins from carbonylation and helps
> >reverse proteasomal decline. As in the aging body, proteolysis declines
in
> >cultured cells as they approach senescence. Australian scientists showed
> >that carnosine enhances intracellular proteolytic activity in human
> >connective tissue cells (Hipkiss AR et al., 1995). Carnosine enhanced
> >proteolysis the most in old cells, and to a lesser extent in "middle
aged"
> >cells, compensating for age-related proteolytic decline (for details see

> >"Carnosine-Nature's pluripotent life extension agent" from this issue).

Chuck

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Nov 30, 2001, 12:09:37 AM11/30/01
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mike <emka...@dodgenet.com> wrote in message news:<9u4sfo$h3m$2...@ins21.netins.net>...

> Man oh man..this is gotta be close!

Has anyone considered ALT-711 as a topical?

mike

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Nov 30, 2001, 1:04:14 AM11/30/01
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I would try it but where do you find it?

mike

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Nov 30, 2001, 1:33:05 AM11/30/01
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"Nuclear" <west...@iprimus.com.au> wrote:
>Mike, a while ago I postulated using the proteolytic enzyme serrapeptase on
>the scalp to get rid of the stuff constricting the follicle. You wrote back
>to me and said to be wary of using proteolytic enzymes on your scalp. Are
>you know changing your mind based on further research? Is it now feasible to
>use proteolytic enzymes like serrapeptase on your scalp and if it is can I
>just crush the pills and mix them in water and apply it? Will the enzyme
>still be "alive", I believe enzymes are tricky things to control.
>
>Thanks.
>
I'm not really sure of this other than the links I furnished in my
post.At first LEF says increased proteolytic activity is good and
has anti-aging properties.Increased proteolytic activity is good for
reversing cross-links or AGE's but will get you increased cell death.
So is cell death good? Yes it can be if the cells are senescent since
senescent cells are stuck in neutral and cause cytokine leakage(Il-1)
to surrounding tissues.
I was also trying to draw something up with cytokines stimulating MHC 2
expression(Kligman study).There indeed maybe something to that.All
cells(maybe not stem) contain MHC antigens.These are for
self recognition.Cells maintain a certain # of these MHC on the
surface.Increased expression of these signal T-cell alarms and they will
increase your odds of autoimmunity.Cancer cells go stealthy and dont
produce these MHC antigens and avoid immune attack.


Final answer:I'm really not sure.I'm only trying to link similar things
together.Two adjacent puzzles pieces in a 3-d puzzle.

Final note:Back in the mid 80's I got this call from a Canadian
doctor.He claimed to have solved balding.His explanation I dont agree
with but perhaps now I think was he talking about proteolytic enzymes.
He said to me that there was a membrane on your scalp which prevented
hair growth.(mid 80's remember).I knew better than that and laughed,
maybe outloud to his explanation.But he said he had 2 enzymes which
he applied topically to dissolve this membrane.I dont know why but
bromelain and papain came to mind.They both are proteolytic enzmes and
can be used for debridement.Never tried the treatment.
Maybe just maybe he was correct? Caveat:there is an otc hair remover
containing papain.I have tried it on the back of my neck and doesnt
work.


Nuclear

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Nov 30, 2001, 4:15:36 AM11/30/01
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What became of this Canadian doctor? Was the membrane he was talking about
the galea? If so isn't it internal? I do recall there was a bald guy in the
Zinc Oxide forum in www.hairsite.com who had a facial peel done and I guess
the person that did it didn't really know where his face ended and his
hairline began and afterwards he noticed hairs growing in the hair zone
parts that were peeled. The hairs later went away after some weeks - the
cause of MPB, whatever that may be, was still in full flight. However this
example seems to illustrate that there is definitely something stifling the
follicle and it can be gotten rid of AND the follicle does not die as some
theorists purport. The question is how to get ris of this stifling? Chemical
peels obviously seem promising, perhaps proteolytic enzymes, perhaps
something radically different? Do you have any further ideas Mike, or
anybody else?

You see, you must never totally write off anbody's new theories or we may
miss the solution, but of course there are loads of snake-oil salesmen out
there and one must be wary.

"mike" <emka...@dodgenet.com> wrote in message

news:9u7971$92l$4...@ins21.netins.net...

mike

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Nov 30, 2001, 5:20:47 AM11/30/01
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"Nuclear" <west...@iprimus.com.au> wrote:
>What became of this Canadian doctor?

Dont know.

Was the membrane he was talking about
>the galea?

Probably he thought it was.IMO it is something similar to the dermal
striae talked about in the Deanol patent.Glucocorticoids cause this too.
Dr.Pickart has something on his website about dermal aging and
subcutaneous fatloss and balding,prolly is very related.

If so isn't it internal? I do recall there was a bald guy in the
>Zinc Oxide forum in www.hairsite.com who had a facial peel done and I guess
>the person that did it didn't really know where his face ended and his
>hairline began and afterwards he noticed hairs growing in the hair zone
>parts that were peeled. The hairs later went away after some weeks - the
>cause of MPB, whatever that may be, was still in full flight.

There's alot we dont know.There's alot more I dont know.Humbleness(realize
you dont know it all then take it from there) and flexibility(drop a
theory in a second no matter how much time you have in it if so called
for) are the keys to successful researching.Avoid bias(as if)
and dont fall in love with your own theories,they'll break your heart.


However this
>example seems to illustrate that there is definitely something stifling the
>follicle and it can be gotten rid of AND the follicle does not die as some
>theorists purport. The question is how to get ris of this stifling? Chemical
>peels obviously seem promising, perhaps proteolytic enzymes, perhaps
>something radically different? Do you have any further ideas Mike, or
>anybody else?

Nope, fresh out.

ERNEST PRIMEAU

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Dec 1, 2001, 12:54:17 AM12/1/01
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What is the matter Mike,your present treatment not working?.Ernie

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