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| manfred95@lycos.com 2006-06-04, 9:15 am |
| I read in a newsletter about cancer that ceramide killed cancer cells
and recomended the amino acid, serine to increase ceramide for
psoriasis. I did a little research and made some notes. (Sorry, I
didn't keep the sources):
One particularly exciting area of apoptosis-related therapy involves
the sphingolipid pathways. The sphingolipids have been shown to be
involved in apoptosis and, in particular ceramide has been shown to
stimulate cell death. This has led to a convincing body of evidence
supporting the concept that increasing ceramide levels represents a
candidate strategy for the treatment of cancer
The molecule sphingosine is synthesized from palmitoyl coenzyme A and
the amino acid serine. Acylation with a fatty acid transferred from a
fatty acyl coenzyme A results in the formation of a ceramide
Ceramide is synthesized in the endoplasmic reticulum from the amino
acid serine
SERINE (Non-Essential Amino Acid) A storage source of glucose by the
liver and muscles; helps strengthen the immune system by providing
antibodies; synthesizes fatty acid sheath around nerve fibers
All sphingolipids are synthesised frm CERAMIDE , which is syn in ER frm
amino acid SERINE - NADPH is required
ceramide is a key mediator of a distinct route to programmed cell
death (PCD), i.e., caspase-independent PCD. Under conditions where
apoptosis is either not initiated or actively inhibited, TNF induces
caspase-independent PCD in L929 fibrosarcoma cells, NIH3T3 fibroblasts,
human leukemic Jurkat T cells, and lung fibroblasts by increasing
intracellular ceramide levels prior to the onset of cell death.
in the TNFa-stimulated pathway of cell death, de novo ceramide
synthesis appears to be necessary for at least part of ceramide
accumulation and subsequent cell death.
These studies underscore the importance of ceramide accumulation in
propagating the cell death signal in response to TNFa and specifically
highlight the role for de novo ceramide synthesis in this process.
Phosphatidyl Serine can only be found in very small amounts from
dietary sources. Phosphatidyl Serine has been shown in numerous
studies to help support positive mood, promote learning and
concentration, help support memory and overall cognitive function and
also help support the body's natural response to certain forms of
stress. (Andrew Lessman Phosphatidyl Serine - PS Benefits)
Serine is a nonessential amino acid, which means that it is
manufactured from other amino acids in the liver; it does not have to
be obtained directly through the diet. Serine stimulates the synthesis
of glucose (blood sugar) in the liver. Serine is known to be the
precursor to cysteine, along with methionine. It is also the precursor
to glycine. Serine works in conjunction with alanine and glycine to
help stabilize blood sugar and provide a timed-release source of
glucose after glycogen depletion. Serine is readily metabolized and
has a wide safety margin. Serine works with choline to help reform
phosphatidylcholine, which is a major component of lecithin.
Serine is an important precursor of tryptophan and serotonin. Previous
studies of patients with chronic fatigue syndrome (CFS) demonstrated
that serine (CFSUM2) was an important urinary metabolite discriminating
between CFS from control subjects, and was negatively correlated with
CFS neurological symptom index and total symptom index. Serine
synthesis requires both alanine and glycine as precursors, and also as
a result of microbial metabolism. These studies showed that the low
urinary excretion of serine in CFS patients reported in previous study
was associated with a disturbed gastrointestinal microbial flora.
Alteration in the aerobic microbial flora, particularly the Gram
negative enteric organisms, may change the exogenous supply of serine
and contribute to the increased symptoms expression of patients with
CFS. Urinary serine levels were checked and found to be low in 7
patients whose illness fitted the CDC criteria for a diagnosis of
Chronic Fatigue Syndrome. A low serine level has previously been
identified as a possible urinary marker (previously known as CFSUM2)
for CFS. Serine was prescribed in a dose of 500mg twice daily to these
people.
Research suggests that low levels of serine may contribute to chronic
fatigue syndrome (CFS) and fibromyalgia (FM). Serine helps produce
immunoglobulins and antibodies for a strong immune system, and also
aids in the absorption of creatine, a substance made from amino acids
that helps build and maintain all the muscles in the body, including
the heart. In order for serine to be manufactured in the body,
sufficient amounts of vitamin B3 and vitamin B6, and folic acid must be
present. Meat and soy foods, dairy products, wheat gluten, and peanuts
are all good natural sources of serine, but today's Western diet
includes so much processed convenience food-amino acid
supplementation may be needed more often than most people realize.
PS may reduce cortisol levels, thereby reducing the impact of stress,
and enhancing exercise recovery and overall immune function
the present data suggest that the dramatic
reduction in ceramide synthesis, which has been found to
bear a significant correlation to the clinical severity, is caused
by a decrease in the activity of serine palmitoyl transferase.
However, the complete relationship between ceramide content
and activity of ceramide-metabolizing enzymes in the
psoriatic skin remains to be clarified.
In conclusion, we demonstrate that the level of ceramide
synthesis is significantly reduced in the lesional epidermis,
which is sensitive enough to make an inverse correlation with
clinical severity in mild to moderate status of psoriasis. We
are not certain whether this finding is primary or secondary
event in psoriasis. However, we suggest that the reduction
of synthetic capacity of ceramide is the important one of the
severity-related factors.
Nicotinamide: a potential addition to the anti-psoriatic weaponry
MOHAMMAD REZA NAMAZI1
Dermatology Department, Shiraz university of Medical Sciences, Shiraz,
Iran
1Correspondence: P.O. Box 71955-687, Shiraz, Iran. E-mail:
namazi_mr@yahoo.com
ABSTRACT
Psoriasis is an inflammatory disorder characterized by a T helper type
1 cell cytokine pattern. Increased expression of adhesion molecules,
prominent neutrophil accumulation, and increased production of nitric
oxide are characteristics of this disorder. Moreover, histamine and
proteases are supposed to participate in the pathogenesis of psoriasis.
Nicotinamide is an inhibitor of poly (ADP-ribose) polymerase-1 (PARP-1)
that, through enhancement of nuclear kappa B-mediated transcription,
plays a pivotal role in the expression of inflammatory cytokines,
chemokines, adhesion molecules, and inflammatory mediators. Through
interaction with CD38 and inhibition of IL-1, IL-12, and TNF-
production, nicotinamide produces a mild TH2 bias. Nicotinamide is a
potent phosphodiesterase inhibitor and suppresses neutrophil chemotaxis
and mast cell histamine release. It inhibits nitric oxide synthase mRNA
induction and suppresses antigen-induced lymphocyte transformation.
Nicotinamide increases the biosynthesis of ceramides, which upon
degradation produce sphingosine. Sphingosine inhibits protein kinase C
(PKC) and decreases basal cell proliferation dependent on PKC. Taken
together, it can be reasoned that nicotinamide could be a useful
addition to anti-psoriatic armamentarium. The combination of
nicotinamide and thalidomide or methotrexate provided a powerful
synergistic inhibition of murine collagen-induced arthritis.
Nicotinamide decreased the methotrexate-induced hepatotoxicity. The
above combinations may prove to have a powerful anti-psoriatic effect
as well. As PARP inhibitors could exert anti-retroviral effect,
nicotinamide could also be of special value in the treatment of
HIV-infected psoriatics.-Namazi, M. R. Nicotinamide: a potential
addition to the anti-psoriatic weaponry.
Nicotinamide increases the biosynthesis of ceramides by keratinocytes
(18) . It is known that the sphingosine derived from degradation of
surface ceramide inhibits protein kinase C (PKC) and decreases basal
cell proliferation dependent on PKC (19) .
Some studies have shown that transient increases in ceramide levels are
associated with the induction of keratinocyte apoptosis (20 , 21) .
This effect could offset the anti-apoptotic effect of nicotinamide
exerted through PARP inhibition
FATTY ACIDS, specifically linoleic acid and gamma linoleic acid, are
required for the skin to retain moisture. Science has found that
linoleic acid is necessary to the enzymatic activity that develops skin
cells into proper water-maintaining barriers.24 A deficiency of
linoleic acid is characteristic of dry skin.25 Studies have found that
a deficiency of linoleic acid is linked to conditions of poor skin such
as acne.26 When applied topically, these two compounds reduce
trans-epidermal water loss.27
Linoleic acid is also a major component of dermal ceramides, the
binding 'mortars' between cells that provide both skin strength and
barrier function.28,29 An animal study found that essential fatty
acid-deficient skin has a weakened water-retaining barrier and that
linoleic acid applied topically metabolizes into ceramides and
unsaturated omega-hydroxy fatty acids, restoring the moisture and
barrier-integrity of the skin.30
The skin-inflammation disorder atopic dermatitis is partially caused by
deficiency in ceramide production and the subsequent weakened barrier
membrane.31
Researchers at the university of California, San Francisco, tested a
topical, ceramide-dominant, lipid-based emollient on 24 children with
atopic dermatitis. After three weeks, 22 children showed a reduction in
trans-epidermal water loss with improvements in skin integrity and
hydration. Improvements continued through six and 21 weeks.33
This supports the hypothesis that a localized insufficiency of linoleic
acid in the follicular epithelium is an etiologic factor in
comedogenesis.(in acne)
In researching this topic, I found that a common problem associated
with eczema and other disorders is the inability of the skin to keep
the deeper layers of the skin from dehydrating. In short, there is
little water in your skin. The missing ingredient is the lipid
ceramide, which we are going to attempt to regenerate in your skin.
| |
| randall 2006-06-04, 9:15 am |
| Hi,
I think we want the pathway on the left iirc.
But we have the one on the right,
http://www.caymanchem.com/images/sc.../cayman2001.jpg
randall.. or do i have it reversed?
manfred95@lycos.com wrote:
> I read in a newsletter about cancer that ceramide killed cancer cells
> and recomended the amino acid, serine to increase ceramide for
> psoriasis. I did a little research and made some notes. (Sorry, I
> didn't keep the sources):
>
> One particularly exciting area of apoptosis-related therapy involves
> the sphingolipid pathways. The sphingolipids have been shown to be
> involved in apoptosis and, in particular ceramide has been shown to
> stimulate cell death. This has led to a convincing body of evidence
> supporting the concept that increasing ceramide levels represents a
> candidate strategy for the treatment of cancer
>
> The molecule sphingosine is synthesized from palmitoyl coenzyme A and
> the amino acid serine. Acylation with a fatty acid transferred from a
> fatty acyl coenzyme A results in the formation of a ceramide
>
> Ceramide is synthesized in the endoplasmic reticulum from the amino
> acid serine
>
> SERINE (Non-Essential Amino Acid) A storage source of glucose by the
> liver and muscles; helps strengthen the immune system by providing
> antibodies; synthesizes fatty acid sheath around nerve fibers
>
> All sphingolipids are synthesised frm CERAMIDE , which is syn in ER frm
> amino acid SERINE - NADPH is required
>
> ceramide is a key mediator of a distinct route to programmed cell
> death (PCD), i.e., caspase-independent PCD. Under conditions where
> apoptosis is either not initiated or actively inhibited, TNF induces
> caspase-independent PCD in L929 fibrosarcoma cells, NIH3T3 fibroblasts,
> human leukemic Jurkat T cells, and lung fibroblasts by increasing
> intracellular ceramide levels prior to the onset of cell death.
>
> in the TNFa-stimulated pathway of cell death, de novo ceramide
> synthesis appears to be necessary for at least part of ceramide
> accumulation and subsequent cell death.
> These studies underscore the importance of ceramide accumulation in
> propagating the cell death signal in response to TNFa and specifically
> highlight the role for de novo ceramide synthesis in this process.
>
> Phosphatidyl Serine can only be found in very small amounts from
> dietary sources. Phosphatidyl Serine has been shown in numerous
> studies to help support positive mood, promote learning and
> concentration, help support memory and overall cognitive function and
> also help support the body's natural response to certain forms of
> stress. (Andrew Lessman Phosphatidyl Serine - PS Benefits)
>
> Serine is a nonessential amino acid, which means that it is
> manufactured from other amino acids in the liver; it does not have to
> be obtained directly through the diet. Serine stimulates the synthesis
> of glucose (blood sugar) in the liver. Serine is known to be the
> precursor to cysteine, along with methionine. It is also the precursor
> to glycine. Serine works in conjunction with alanine and glycine to
> help stabilize blood sugar and provide a timed-release source of
> glucose after glycogen depletion. Serine is readily metabolized and
> has a wide safety margin. Serine works with choline to help reform
> phosphatidylcholine, which is a major component of lecithin.
>
> Serine is an important precursor of tryptophan and serotonin. Previous
> studies of patients with chronic fatigue syndrome (CFS) demonstrated
> that serine (CFSUM2) was an important urinary metabolite discriminating
> between CFS from control subjects, and was negatively correlated with
> CFS neurological symptom index and total symptom index. Serine
> synthesis requires both alanine and glycine as precursors, and also as
> a result of microbial metabolism. These studies showed that the low
> urinary excretion of serine in CFS patients reported in previous study
> was associated with a disturbed gastrointestinal microbial flora.
> Alteration in the aerobic microbial flora, particularly the Gram
> negative enteric organisms, may change the exogenous supply of serine
> and contribute to the increased symptoms expression of patients with
> CFS. Urinary serine levels were checked and found to be low in 7
> patients whose illness fitted the CDC criteria for a diagnosis of
> Chronic Fatigue Syndrome. A low serine level has previously been
> identified as a possible urinary marker (previously known as CFSUM2)
> for CFS. Serine was prescribed in a dose of 500mg twice daily to these
> people.
>
> Research suggests that low levels of serine may contribute to chronic
> fatigue syndrome (CFS) and fibromyalgia (FM). Serine helps produce
> immunoglobulins and antibodies for a strong immune system, and also
> aids in the absorption of creatine, a substance made from amino acids
> that helps build and maintain all the muscles in the body, including
> the heart. In order for serine to be manufactured in the body,
> sufficient amounts of vitamin B3 and vitamin B6, and folic acid must be
> present. Meat and soy foods, dairy products, wheat gluten, and peanuts
> are all good natural sources of serine, but today's Western diet
> includes so much processed convenience food-amino acid
> supplementation may be needed more often than most people realize.
>
> PS may reduce cortisol levels, thereby reducing the impact of stress,
> and enhancing exercise recovery and overall immune function
>
> the present data suggest that the dramatic
> reduction in ceramide synthesis, which has been found to
> bear a significant correlation to the clinical severity, is caused
> by a decrease in the activity of serine palmitoyl transferase.
> However, the complete relationship between ceramide content
> and activity of ceramide-metabolizing enzymes in the
> psoriatic skin remains to be clarified.
> In conclusion, we demonstrate that the level of ceramide
> synthesis is significantly reduced in the lesional epidermis,
> which is sensitive enough to make an inverse correlation with
> clinical severity in mild to moderate status of psoriasis. We
> are not certain whether this finding is primary or secondary
> event in psoriasis. However, we suggest that the reduction
> of synthetic capacity of ceramide is the important one of the
> severity-related factors.
>
> Nicotinamide: a potential addition to the anti-psoriatic weaponry
> MOHAMMAD REZA NAMAZI1
> Dermatology Department, Shiraz university of Medical Sciences, Shiraz,
> Iran
> 1Correspondence: P.O. Box 71955-687, Shiraz, Iran. E-mail:
> namazi_mr@yahoo.com
> ABSTRACT
> Psoriasis is an inflammatory disorder characterized by a T helper type
> 1 cell cytokine pattern. Increased expression of adhesion molecules,
> prominent neutrophil accumulation, and increased production of nitric
> oxide are characteristics of this disorder. Moreover, histamine and
> proteases are supposed to participate in the pathogenesis of psoriasis.
> Nicotinamide is an inhibitor of poly (ADP-ribose) polymerase-1 (PARP-1)
> that, through enhancement of nuclear kappa B-mediated transcription,
> plays a pivotal role in the expression of inflammatory cytokines,
> chemokines, adhesion molecules, and inflammatory mediators. Through
> interaction with CD38 and inhibition of IL-1, IL-12, and TNF-
> production, nicotinamide produces a mild TH2 bias. Nicotinamide is a
> potent phosphodiesterase inhibitor and suppresses neutrophil chemotaxis
> and mast cell histamine release. It inhibits nitric oxide synthase mRNA
> induction and suppresses antigen-induced lymphocyte transformation.
> Nicotinamide increases the biosynthesis of ceramides, which upon
> degradation produce sphingosine. Sphingosine inhibits protein kinase C
> (PKC) and decreases basal cell proliferation dependent on PKC. Taken
> together, it can be reasoned that nicotinamide could be a useful
> addition to anti-psoriatic armamentarium. The combination of
> nicotinamide and thalidomide or methotrexate provided a powerful
> synergistic inhibition of murine collagen-induced arthritis.
> Nicotinamide decreased the methotrexate-induced hepatotoxicity. The
> above combinations may prove to have a powerful anti-psoriatic effect
> as well. As PARP inhibitors could exert anti-retroviral effect,
> nicotinamide could also be of special value in the treatment of
> HIV-infected psoriatics.-Namazi, M. R. Nicotinamide: a potential
> addition to the anti-psoriatic weaponry.
>
> Nicotinamide increases the biosynthesis of ceramides by keratinocytes
> (18) . It is known that the sphingosine derived from degradation of
> surface ceramide inhibits protein kinase C (PKC) and decreases basal
> cell proliferation dependent on PKC (19) .
>
> Some studies have shown that transient increases in ceramide levels are
> associated with the induction of keratinocyte apoptosis (20 , 21) .
> This effect could offset the anti-apoptotic effect of nicotinamide
> exerted through PARP inhibition
>
>
> FATTY ACIDS, specifically linoleic acid and gamma linoleic acid, are
> required for the skin to retain moisture. Science has found that
> linoleic acid is necessary to the enzymatic activity that develops skin
> cells into proper water-maintaining barriers.24 A deficiency of
> linoleic acid is characteristic of dry skin.25 Studies have found that
> a deficiency of linoleic acid is linked to conditions of poor skin such
> as acne.26 When applied topically, these two compounds reduce
> trans-epidermal water loss.27
> Linoleic acid is also a major component of dermal ceramides, the
> binding 'mortars' between cells that provide both skin strength and
> barrier function.28,29 An animal study found that essential fatty
> acid-deficient skin has a weakened water-retaining barrier and that
> linoleic acid applied topically metabolizes into ceramides and
> unsaturated omega-hydroxy fatty acids, restoring the moisture and
> barrier-integrity of the skin.30
> The skin-inflammation disorder atopic dermatitis is partially caused by
> deficiency in ceramide production and the subsequent weakened barrier
> membrane.31
> Researchers at the university of California, San Francisco, tested a
> topical, ceramide-dominant, lipid-based emollient on 24 children with
> atopic dermatitis. After three weeks, 22 children showed a reduction in
> trans-epidermal water loss with improvements in skin integrity and
> hydration. Improvements continued through six and 21 weeks.33
> This supports the hypothesis that a localized insufficiency of linoleic
> acid in the follicular epithelium is an etiologic factor in
> comedogenesis.(in acne)
>
> In researching this topic, I found that a common problem associated
> with eczema and other disorders is the inability of the skin to keep
> the deeper layers of the skin from dehydrating. In short, there is
> little water in your skin. The missing ingredient is the lipid
> ceramide, which we are going to attempt to regenerate in your skin.
| |
| manfred95@lycos.com 2006-06-04, 9:15 am |
| These researchers believe the reduction in the ceramide level
associates
with downregulation of the apoptotic pathway resulting
in epidermal proliferation in psoriasis.
Make note of the "serine palmitoyl transferase" necessary for the
generation of ceramide in psoriatic skin in this study. Serine
interested me since it is also shown to be deficient in CFS.
Exerpts from:
http://jkms.kams.or.kr/2006/pdf/02095.pdf
Ceramides and Cell Signaling Molecules in Psoriatic Epidermis:
Reduced Levels of Ceramides, PKC- , and JNK
......Decreased levels of ceramides have been associated with
skin conditions involving dryness and barrier disruption,
such as psoriasis, atopic dermatitis, and xerosis (12, 13). In
this study, the levels of ceramides were decreased significantly
in psoriatic epidermis. The level of ceramides in the epidermis
results from the balance between the activities of ceramide-
generating enzymes, such as serine palmitoyl transferase
in the de novo synthesis pathway and sphingomyelinase, and
the activities of degradative enzymes, such as ceramidase (14-
17).....
DISCUSSION
Decreased levels of ceramides have been reported in skin
conditions involving dryness and barrier disruption, such as
psoriasis. Moreover, the importance of ceramides in the epidermal
lipid barrier has been documented repeatedly (1, 3-
5). In terms of the apoptotic pathway, however, there are few
investigations of ceramides and related apoptotic signals in
psoriatic epidermis. This study showed that the level of ceramides
was significantly reduced with concomitant decreases in
PKC- and JNK in lesional epidermis of patients with
psoriasis.
Decreased levels of ceramides have been associated with
skin conditions involving dryness and barrier disruption,
such as psoriasis, atopic dermatitis, and xerosis (12, 13). In
this study, the levels of ceramides were decreased significantly
in psoriatic epidermis. The level of ceramides in the epidermis
results from the balance between the activities of ceramide-
generating enzymes, such as serine palmitoyl transferase
in the de novo synthesis pathway and sphingomyelinase, and
the activities of degradative enzymes, such as ceramidase (14-
17). Previously, we observed that the levels of ceramides were
decreased, while those of diacylglycerol were increased (13).
In addition, no alteration in the ceramidase level was detected.
It is understood that the sphingomyelin pathway is initiated
by the hydrolysis of sphingomyelin by sphingomyelinase
(18). Together with these findings, the present data
suggest that the dramatic reduction in the ceramide level,
which is significantly correlated with the clinical severity, is
caused by a decrease in the activity of sphingomyelinase.
However, the complete relationship between the ceramide
content and the activity of ceramide-metabolizing enzymes
in the psoriatic skin remains to be clarified.
We observed decreased levels of PKC- and JNK expression
in lesional epidermis with psoriasis, together with decreased
levels of ceramides. This suggests that the decreased
level of ceramides induced downregulation of the apoptotic
signaling pathway in the psoriatic epidermis. These results
are in concordance with the findings of earlier studies, in
which the level of PKC- expression was decreased in psoriatic
epidermis (19, 20). However, no correlation was observed
between the expression levels of PKC- and JNK and the
PASI score in mild to moderate psoriasis.
Ceramides induce the activation of apoptotic cell-signaling
molecules, such as PKC- and JNK. In addition, sphingomyelinase-
induced ceramide generation is stimulated
by PKC- and JNK activation (20, 21). Hence, this suggests
that decreased ceramide levels lead to the downregulation of
PKC- and JNK, which in turn downregulates sphingomyelinase-
induced ceramide generation and ultimately induces
the anti-apoptotic and proliferative characteristics of psoriatic
epidermis.
In conclusion, we demonstrated that 1) the level of ceramides
was reduced significantly in lesional epidermis with
psoriasis, 2) this decrease was associated with the downregulation
of apoptotic signaling molecules, such as PKC- and
JNK, and 3) there was a significant correlation between the
ceramide level and the clinical severity in mild to moderate
psoriasis. We are not certain whether this finding is a primary
or secondary event in psoriasis. However, we suggest
that the reduction in the ceramide level not only induces a
defect in water retention and barrier function but also associates
with downregulation of the apoptotic pathway resulting
in epidermal proliferation in psoriasis.
| |
| randall 2006-06-04, 9:15 am |
|
manfred95@lycos.com wrote:
> These researchers believe the reduction in the ceramide level
> associates
> with downregulation of the apoptotic pathway resulting
> in epidermal proliferation in psoriasis.
>
> Make note of the "serine palmitoyl transferase" necessary for the
> generation of ceramide in psoriatic skin in this study. Serine
> interested me since it is also shown to be deficient in CFS.
Ok,
http://www.google.com/search?hl=en&...ine&btnG=Search
Since i've got craP on the brain now, i tossed it into the mix.
(see P ng thread-- *cellcept is it working?* -MForget post/ JXStern
post/randall post)
>
> Exerpts from:
>
> http://jkms.kams.or.kr/2006/pdf/02095.pdf
> Ceramides and Cell Signaling Molecules in Psoriatic Epidermis:
> Reduced Levels of Ceramides, PKC- , and JNK
>
> .....Decreased levels of ceramides have been associated with
> skin conditions involving dryness and barrier disruption,
> such as psoriasis, atopic dermatitis, and xerosis (12, 13). In
> this study, the levels of ceramides were decreased significantly
> in psoriatic epidermis. The level of ceramides in the epidermis
> results from the balance between the activities of ceramide-
> generating enzymes, such as serine palmitoyl transferase
> in the de novo synthesis pathway and sphingomyelinase, and
> the activities of degradative enzymes, such as ceramidase (14-
> 17).....
Sounds like it's downstream of an initial event. A primary one?
Oh what could that be? Darn if it's not a gene thing. lol
Yet, what can we do to stoP it?
>
> DISCUSSION
> Decreased levels of ceramides have been reported in skin
> conditions involving dryness and barrier disruption, such as
> psoriasis. Moreover, the importance of ceramides in the epidermal
> lipid barrier has been documented repeatedly (1, 3-
> 5). In terms of the apoptotic pathway, however, there are few
> investigations of ceramides and related apoptotic signals in
> psoriatic epidermis. This study showed that the level of ceramides
> was significantly reduced with concomitant decreases in
> PKC- and JNK in lesional epidermis of patients with
> psoriasis.
> Decreased levels of ceramides have been associated with
> skin conditions involving dryness and barrier disruption,
> such as psoriasis, atopic dermatitis, and xerosis (12, 13). In
> this study, the levels of ceramides were decreased significantly
> in psoriatic epidermis. The level of ceramides in the epidermis
> results from the balance between the activities of ceramide-
> generating enzymes, such as serine palmitoyl transferase
> in the de novo synthesis pathway and sphingomyelinase, and
> the activities of degradative enzymes, such as ceramidase (14-
> 17). Previously, we observed that the levels of ceramides were
> decreased, while those of diacylglycerol were increased (13).
> In addition, no alteration in the ceramidase level was detected.
> It is understood that the sphingomyelin pathway is initiated
> by the hydrolysis of sphingomyelin by sphingomyelinase
> (18). Together with these findings, the present data
> suggest that the dramatic reduction in the ceramide level,
> which is significantly correlated with the clinical severity, is
> caused by a decrease in the activity of sphingomyelinase.
> However, the complete relationship between the ceramide
> content and the activity of ceramide-metabolizing enzymes
> in the psoriatic skin remains to be clarified.
> We observed decreased levels of PKC- and JNK expression
> in lesional epidermis with psoriasis, together with decreased
> levels of ceramides. This suggests that the decreased
> level of ceramides induced downregulation of the apoptotic
> signaling pathway in the psoriatic epidermis. These results
> are in concordance with the findings of earlier studies, in
> which the level of PKC- expression was decreased in psoriatic
> epidermis (19, 20). However, no correlation was observed
> between the expression levels of PKC- and JNK and the
> PASI score in mild to moderate psoriasis.
> Ceramides induce the activation of apoptotic cell-signaling
> molecules, such as PKC- and JNK. In addition, sphingomyelinase-
> induced ceramide generation is stimulated
> by PKC- and JNK activation (20, 21). Hence, this suggests
> that decreased ceramide levels lead to the downregulation of
> PKC- and JNK, which in turn downregulates sphingomyelinase-
> induced ceramide generation and ultimately induces
> the anti-apoptotic and proliferative characteristics of psoriatic
> epidermis.
> In conclusion, we demonstrated that 1) the level of ceramides
> was reduced significantly in lesional epidermis with
> psoriasis, 2) this decrease was associated with the downregulation
> of apoptotic signaling molecules, such as PKC- and
> JNK, and 3) there was a significant correlation between the
> ceramide level and the clinical severity in mild to moderate
> psoriasis. We are not certain whether this finding is a primary
> or secondary event in psoriasis. However, we suggest
> that the reduction in the ceramide level not only induces a
> defect in water retention and barrier function but also associates
> with downregulation of the apoptotic pathway resulting
> in epidermal proliferation in psoriasis.
Isn't this a second messenger thing again? Just like in the cellcept
thread?
YeP!
Trying a pkc and jnk with C-GmP google (took the serine out),
http://www.google.com/search?q=pkc%...rch&sa=N&tab=gw
I wonder if the second message to NOT eat MEAT is sinking in?
LOL
Today is to much fun, meet me at the dead sea Oasis inn for a
hamburger! ;-/
The NB-uvb's will protect us!
What did the Israeli PM say? Courage and be strong?
But, won't additional digestive enzymes just make more C-gm P's?
Or are they the result of faulty digestion? More bile,
http://www.bbc.co.uk/schools/gcsebi...stionrev7.shtml
OK ok.... put me in a gulaG and starve me!
Where's a lifestyle when you want one? Free to be me without P? And
able to eat uP life without strife?
randall... never shall the P twain meat? Or with IP6 i be free?
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