| NeurosCIeNCe | artiCLe of pruritus (like histamine and inflammatory cytokines)9 .
In response to environmental stressors, protein kinases phosphorylate eukaryotic initiation factor 2 (eIF2), which then either alleviates cellular injury or induces apoptosis10
Tyrosinase . The generation of No can upstream induce
and downstream mediate the kinases that phosphorylate the alpha subunit of eIF2, which plays a crucial role in regulating gene expression. The production of No and activation of eIF2 alpha kinases coordinate to regulate physiological and pathological events, such as innate immune response11
. No seems to be implicated, with calcium, in
mitochondria biogenesis. No may bind to cytochrome c oxidase (CoX) and reversibly inhibit mitochondrial chain respiration by competing with oxygen12
. In one study, uVB was shown to significantly
increase the expression of cytokine-inducible No synthesis (iNos) in the skin at 6 hours post-irradiation13
.
Fortunately, estradiol (e2) has been shown to increase neuronal Nos (nNos) protein expression. Following the menopause, the drop in e2 leads to a reduced vasodilatory capacity of resistant microvessels and less cell nutrition14
Dopachrome
Dopachrome oxydase
Hydroxyindoles Mixed Eumelanins , while collagen fibroblast expression
also decreases. Therefore, having sufficient e2 levels after the menopause can be of great use for skin repair and maintenance.
Dopamine dopamine receptors are involved in the homeostasis of the skin’s layers, particularly in the keratinocytes15
Figure 3 Glutathion reduces melanin
Tetrahydrobiopterin Tetrahydrobiopterin (Bh4
. Indeed,
dopamine is present everywhere in the human body (e.g. gut, skin, brain, heart). If an antagonist is applied, such as bromocryptine, hyperproliferation of the epidermis can be quickly reduced or avoided altogether. Metabolites of dopaquinone, eumelanin and
pheomelanin require glutathione, which needs to be in sufficient quantity in order to avoid cellular damage. It is important to recognise the link between neurotransmitters and the protectors against cellular oxidation, such as glutathione (or superoxide dismutase (sod)). one role of dopamine is to polymerise actin, which
participates in the cellular cytoskeleton. dopamine passes through the phospholipid membrane and directly polymerises G-actin, inducing the appearance of a network of actin filament16
Molecule of the neurotransmitter dopamine
) is an important cofactor in a
number of enzymatic systems: phenylalanine to tyrosine, tyrosine to dopamine, and in the chain leading from L-tryptophan to serotonin and melatonin17
. Bh4
All forms of oxidation, no matter the source, increase oxidation, causing lower tyrosine hydroxylase
activity and more vascular constriction, which lowers skin temperature. This can be seen clearly in the skin of older people. Bh4
is also involved in the metabolism of homocysteine, thus in the
process of methylation, dNA repair, and the natural process of inactive genes. Its cofactor is folic acid which,
like copper, is indispensable. Bh4
augments reflex
vasoconstriction in aged skin, although this appears to occur through
its role in noradrenaline biosynthesis. While Bh4
has not been directly . Insulin and oestrogens are carriers of
actin, which dopamine helps to structure. dopamine production requires a sufficient content of vitamins, particularly B3, B6, B9 and C. Nutrients also have a role to play here, significantly iron, with which thyroid hormones interact to increase the production of dopamine. Copper should not be neglected as a contributing factor for enzymes. Both copper and vitamin d are central to regulate dopamine production in the skin. Glutathione has been used in
this way for a long time and with success, in order to whiten the skin either orally or via injection, particularly for Asian skin.
measured in human skin, its concentration is diminished in other aged tissues and this has been linked to oxidative
stress at various points along the Bh4 biosynthetic and salvage pathways18
. cells19 adrenocorticotropic hormone
Melanocytes are considered neuroendocrine capable (via uVBs) of synthesising (ACTh),
melanocyte-stimulating hormone (Msh), steroids, dopamine, and serotonin, and therefore melatonin and the thyroid hormones. Melanocytes appear as
an extremely sensitive system to external and internal disturbances, capable of alerting the local and distant structures (such as the brain), and of coordinating responses. Their role in the regulation of skin neurotransmitters and local hormones, or neurohormones, is greater than was first hypothesised.
prime-journal.com | July 2011 ❚ 55 melanines Pheomelanins Cysteine
Intermediary benzothiazines
Tyrosinase
L – Tyrosine O2
L – Dopa O2 Dopaquinone
Glutathione Glutathione reductase
Reduced glutathione Glutathione Dopa
7 – glutamyltranspeptidase Cysteinyl Dopa
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