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2007-9-2 9:57:31

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Editor's note: Please note that just because your skin has a tendency to repair or protect against damage caused by ultraviolet rays does not mean UV rays won’t cause any harm. In a word, UV causes damage to the skin and people need to avoid excessive exposure to ultraviolet rays no matter they come from the sun or not.






There is a reason for the skin to become dark brown after it’s exposed to the sunshine.   Tanning induced by ultraviolet rays plays a role in protecting against the development of skin cancer, namely melanoma, the fastest growing form of cancer in the world, according to a new study.


Early studies have linked exposure to sunshine rays to increased risk of skin cancer. But the new study suggests that when the skin is exposed to sun rays, a protein known as the “master watchman of the genome” is triggered to guard against cancer-causing DNA damage, which would otherwise lead to the development of skin cancer.


In addition, the study reported in the March 9 issue of the journal Cell by researchers from Dana-Farber Cancer Institute suggested that the protein, p53 also may play a role in people’s desire to be exposed to the sunshine, which can reduce one’s risk of melanoma by promoting tanning.


A scientist with foodconsumer.org said that the role of the sunshine or Ultraviolet rays may be more than just protecting against melanoma as early studies have associated sun exposure to reduced risk of a number of other cancers although some researchers attribute such a protective effect to the increased level of vitamin D.


“The number one risk factor for melanoma is an inability to tan; people who tan easily or have dark pigmentation are far less likely to develop the disease,” says the study’s senior author, David E. Fisher, MD, PhD, director of the Melanoma Program at Dana-Farber and a professor in pediatrics at Children's Hospital Boston.


“This study suggests that p53, one of the best-known tumor-suppressor proteins in our body, has a powerful role in protecting us against sun damage in the skin.”


Earlier last year, Fisher and his colleagues published a study revealing that ultraviolet (UV) radiation from the sun triggers the secretion of a hormone called α-MSH in skin cells, which attaches to nearby skin cells called melanocytes, promoting the production of a skin-darkening pigment called melanin.


But it has been unknown how production of α-MSH is increased although investigators knew it is created when another protein known as opiomelanocortin or POMC was split apart.   They also knew sun rays increase POMC in cells. But what causes the increase in POMC remained unclear.


The answer might be protein P53, according to Fisher and colleagues.   A gene analysis showed that PMOC proteins meshed well with p53, leading the researchers to speculate that there was a possibility that when p53 docks well, POMC production increases.


Studies of human and mouse keratinocytes showed that 6-hour exposure of the cells to UV radiation drastically increased both POMC and p53, leading to an increase in α-MSH by a factor of 30 times compared to the cells unexposed.


Further evidence supported the p53's role in tanning.    When p53 was inserted into keratinocytes, POMC increased drastically.   In contrast, mice without p53 in the cells did not experience POMC increase and the mice did not tan.


The p53 theory may also explain the common skin condition or the development of small dark spots, which is caused by stress or irritation of the skin, but not ultraviolet rays and is common among elderly people.   The condition is not dangerous, but renders a negative cosmetic effect.


“Our research offers a potential explanation of how this condition – known as post-inflammatory hyper-pigmentation, or age spots – occurs,” Fisher says.


“We know that it occurs as a result of stress, and p53 is a classic ‘stress’ protein, going into action when cells experience stress-related DNA damage. What we’ve learned about p53 suggests that it may trigger the hyperpigmentation process.”


The researchers also said that the same process that causes PMOC to increase production of α-MSH, which leads to the protection against melanoma, may also causes the production of β-endorphin, which binds to the body's opiate receptor associated with perception of feelings of pleasure.


This theory explains why people often get addicted to exposure to sunshine.


“Even as p53 is causing skin to tan during sunlight exposure, it may also affect neuronal circuits,” Fisher says.


“These proteins may provide an explicit link between the regulation of tanning and of mood. It raises the question of whether p53-mediated induction of β-endorphin is involved in sun-seeking behavior, which often increases skin cancer risk.”




Further readings:


Li L, Hu DN, Zhao H, McCormick SA, Nordlund JJ, Boissy RE. Uveal melanocytes do not respond to or express receptors for alpha-melanocyte-stimulating hormone.
Invest Ophthalmol Vis Sci. 2006 Oct;47(10):4507-12.










D'Orazio JA, Nobuhisa T, Cui R, Arya M, Spry M, Wakamatsu K, Igras V, Kunisada T, Granter SR, Nishimura EK, Ito S, Fisher DE. Topical drug rescue strategy and skin protection based on the role of Mc1r in UV-induced tanning.
Nature. 2006 Sep 21;443(7109):340-4.


Barnetson RS, Ooi TK, Zhuang L, Halliday GM, Reid CM, Walker PC, Humphrey SM, Kleinig MJ. [Nle4-D-Phe7]-alpha-melanocyte-stimulating hormone significantly increased pigmentation and decreased UV damage in fair-skinned Caucasian volunteers.
J Invest Dermatol. 2006 Aug;126(8):1869-78. Epub 2006 Jun 8.


Abdel-Malek ZA, Kadekaro AL, Kavanagh RJ, Todorovic A, Koikov LN, McNulty JC, Jackson PJ, Millhauser GL, Schwemberger S, Babcock G, Haskell-Luevano C, Knittel JJ. Melanoma prevention strategy based on using tetrapeptide alpha-MSH analogs that protect human melanocytes from UV-induced DNA damage and cytotoxicity.
FASEB J. 2006 Jul;20(9):1561-3. Epub 2006 May 24.


Eves PC, MacNeil S, Haycock JW. alpha-Melanocyte stimulating hormone, inflammation and human melanoma.
Peptides. 2006 Feb;27(2):444-52. Epub 2005 Nov 4. Review.


Kadekaro AL, Kavanagh R, Kanto H, Terzieva S, Hauser J, Kobayashi N, Schwemberger S, Cornelius J, Babcock G, Shertzer HG, Scott G, Abdel-Malek ZA. alpha-Melanocortin and endothelin-1 activate antiapoptotic pathways and reduce DNA damage in human melanocytes.
Cancer Res. 2005 May 15;65(10):4292-9.


Pichler R, Crespillo C, Maschek W, Esteva I, Soriguer F, Sfetsos K, Aubock J. Plasma levels of alpha-melanotropin and ACTH-like immunoreactivities do not vary by season or skin type in women from southern and central Europe.
Neuropeptides. 2004 Oct;38(5):325-30.


Dorr RT, Ertl G, Levine N, Brooks C, Bangert JL, Powell MB, Humphrey S, Alberts DS. Effects of a superpotent melanotropic peptide in combination with solar UV radiation on tanning of the skin in human volunteers.
Arch Dermatol. 2004 Jul;140(7):827-35.


Bohm M, Luger TA. [Alpha-melanocyte-stimulating hormone. Its current significance for dermatology]
Hautarzt. 2004 May;55(5):436-45. Review. German.


Kadekaro AL, Kanto H, Kavanagh R, Abdel-Malek ZA. Significance of the melanocortin 1 receptor in regulating human melanocyte pigmentation, proliferation, and survival.
Ann N Y Acad Sci. 2003 Jun;994:359-65. Review.


Leonard JH, Marks LH, Chen W, Cook AL, Boyle GM, Smit DJ, Brown DL, Stow JL, Parsons PG, Sturm RA. Screening of human primary melanocytes of defined melanocortin-1 receptor genotype: pigmentation marker, ultrastructural and UV-survival studies.
Pigment Cell Res. 2003 Jun;16(3):198-207.


Lassalle MW, Igarashi S, Sasaki M, Wakamatsu K, Ito S, Horikoshi T. Effects of melanogenesis-inducing nitric oxide and histamine on the production of eumelanin and pheomelanin in cultured human melanocytes.
Pigment Cell Res. 2003 Feb;16(1):81-4.


Gambichler T, Bader A, Vojvodic M, Avermaete A, Schenk M, Altmeyer P, Hoffmann K. Plasma levels of opioid peptides after sunbed exposures.
Br J Dermatol. 2002 Dec;147(6):1207-11.


Kalden DH, Brzoska T, Schwarz T, Richard A, Rougier A, Luger TA.
Eur J Dermatol. 2002 Jul-Aug;12(4):XV-XVI.
UV-induced production of immunosuppressive mediators in human skin: prevention by a broadspectrum sunscreen.

Scott MC, Wakamatsu K, Ito S, Kadekaro AL, Kobayashi N, Groden J, Kavanagh R, Takakuwa T, Virador V, Hearing VJ, Abdel-Malek ZA. Human melanocortin 1 receptor variants, receptor function and melanocyte response to UV radiation.
J Cell Sci. 2002 Jun 1;115(Pt 11):2349-55.


Pavey S, Gabrielli B. Alpha-melanocyte stimulating hormone potentiates p16/CDKN2A expression in human skin after ultraviolet irradiation.
Cancer Res. 2002 Feb 1;62(3):875-80.


Tsatmali M, Ancans J, Thody AJ. Melanocyte function and its control by melanocortin peptides.
J Histochem Cytochem. 2002 Feb;50(2):125-33. Review.


Virador VM, Muller J, Wu X, Abdel-Malek ZA, Yu ZX, Ferrans VJ, Kobayashi N, Wakamatsu K, Ito S, Hammer JA, Hearing VJ Influence of alpha-melanocyte-stimulating hormone and ultraviolet radiation on the transfer of melanosomes to keratinocytes.
FASEB J. 2002 Jan;16(1):105-7. Epub 2001 Nov 29..


Schaffer JV, Bolognia JL. The melanocortin-1 receptor: red hair and beyond.
Arch Dermatol. 2001 Nov;137(11):1477-85. Review.


Wintzen M, de Winter S, Out-Luiting JJ, van Duinen SG, Vermeer BJ.
Exp Dermatol. 2001 Oct;10(5):305-11.
Presence of immunoreactive beta-endorphin in human skin.

Pawelek JM. Approaches to increasing skin melanin with MSH analogs and synthetic melanins.
Pigment Cell Res. 2001 Jun;14(3):155-60. Review.


Slominski A, Wortsman J. Neuroendocrinology of the skin.
Endocr Rev. 2000 Oct;21(5):457-87. Review. Erratum in: Endocr Rev 2002 Jun;23(3):364.


Tsatmali M, Ancans J, Yukitake J, Thody AJ. Skin POMC peptides: their actions at the human MC-1 receptor and roles in the tanning response.
Pigment Cell Res. 2000;13 Suppl 8:125-9.


Scholzen TE, Brzoska T, Kalden DH, Hartmeyer M, Fastrich M, Luger TA, Armstrong CA, Ansel JC. Expression of functional melanocortin receptors and proopiomelanocortin peptides by human dermal microvascular endothelial cells.
Ann N Y Acad Sci. 1999 Oct 20;885:239-53. Review.


Luger TA, Schwarz T, Kalden H, Scholzen T, Schwarz A, Brzoska T. Role of epidermal cell-derived alpha-melanocyte stimulating hormone in ultraviolet light mediated local immunosuppression.
Ann N Y Acad Sci. 1999 Oct 20;885:209-16. Review.




Abdel-Malek Z, Suzuki I, Tada A, Im S, Akcali C. The melanocortin-1 receptor and human pigmentation.
Ann N Y Acad Sci. 1999 Oct 20;885:117-33. Review.


Chakraborty AK, Funasaka Y, Slominski A, Bolognia J, Sodi S, Ichihashi M, Pawelek JM. UV light and MSH receptors.
Ann N Y Acad Sci. 1999 Oct 20;885:100-16. Review.


Scholzen TE, Brzoska T, Kalden DH, O'Reilly F, Armstrong CA, Luger TA, Ansel JC. Effect of ultraviolet light on the release of neuropeptides and neuroendocrine hormones in the skin: mediators of photodermatitis and cutaneous inflammation.
J Investig Dermatol Symp Proc. 1999 Sep;4(1):55-60. Review.




Thody AJ, Graham A. Does alpha-MSH have a role in regulating skin pigmentation in humans?
Pigment Cell Res. 1998 Oct;11(5):265-74. Review.




Dissanayake NS, Mason RS. Modulation of skin cell functions by transforming growth factor-beta1 and ACTH after ultraviolet irradiation.
J Endocrinol. 1998 Oct;159(1):153-63.


Funasaka Y, Chakraborty AK, Hayashi Y, Komoto M, Ohashi A, Nagahama M, Inoue Y, Pawelek J, Ichihashi M. Modulation of melanocyte-stimulating hormone receptor expression on normal human melanocytes: evidence for a regulatory role of ultraviolet B, interleukin-1alpha, interleukin-1beta, endothelin-1 and tumour necrosis factor-alpha.
Br J Dermatol. 1998 Aug;139(2):216-24.




Redondo P, Garcia-Foncillas J, Okroujnov I, Bandres E. Alpha-MSH regulates interleukin-10 expression by human keratinocytes.
Arch Dermatol Res. 1998 Aug;290(8):425-8.








Luger TA. Immunomodulation by UV light: role of neuropeptides.
Eur J Dermatol. 1998 Apr-May;8(3):198-9. Review.


Bayerl C, Lauk J, Moll I, Jung EG. Immunohistochemical characterization of HSP, alpha-MSH, Merkel cells and neuronal markers in acute UV dermatitis and acute contact dermatitis in vivo.
Inflamm Res. 1997 Oct;46(10):409-11.

Luger TA, Scholzen T, Grabbe S. The role of alpha-melanocyte-stimulating hormone in cutaneous biology.
J Investig Dermatol Symp Proc. 1997 Aug;2(1):87-93. Review.


Hill HZ, Li W, Xin P, Mitchell DL. Melanin: a two edged sword?
Pigment Cell Res. 1997 Jun;10(3):158-61. Review.


Li W, Hill HZ. Induced melanin reduces mutations and cell killing in mouse melanoma.
Photochem Photobiol. 1997 Mar;65(3):480-5.


Eller MS, Ostrom K, Gilchrest BA. DNA damage enhances melanogenesis.
Proc Natl Acad Sci U S A. 1996 Feb 6;93(3):1087-92.


Gilchrest BA, Park HY, Eller MS, Yaar M. Mechanisms of ultraviolet light-induced pigmentation.
Photochem Photobiol. 1996 Jan;63(1):1-10. Review.




Kiss M, Wlaschek M, Brenneisen P, Michel G, Hommel C, Lange TS, Peus D, Kemeny L, Dobozy A, Scharffetter-Kochanek K, et al. Alpha-melanocyte stimulating hormone induces collagenase/matrix metalloproteinase-1 in human dermal fibroblasts.
Biol Chem Hoppe Seyler. 1995 Jul;376(7):425-30.


Iyengar B. Corticotropin expression by human melanocytes in the skin.
Pigment Cell Res. 1995 Jun;8(3):142-6.


Pawelek JM, Chakraborty AK, Osber MP, Orlow SJ, Min KK, Rosenzweig KE, Bolognia JL. Molecular cascades in UV-induced melanogenesis: a central role for melanotropins?
Pigment Cell Res. 1992 Nov;5(5 Pt 2):348-56. Review.


Jimbow K, Alena F, Dixon W, Hara H. Regulatory factors of pheo- and eumelanogenesis in melanogenic compartments.
Pigment Cell Res. 1992;Suppl 2:36-42. Review.


Friedmann PS, Wren F, Buffey J, Macneil S. Alpha-MSH causes a small rise in cAMP but has no effect on basal or ultraviolet-stimulated melanogenesis in human melanocytes.
Br J Dermatol. 1990 Aug;123(2):145-51.


Seechurn P, Thody AJ. The effect of ultraviolet radiation and melanocyte-stimulating hormone on tyrosinase activity in epidermal melanocytes of the mouse.
J Dermatol Sci. 1990 Jul;1(4):283-8.


Remy W, Rakoski J, von Mayenburg J. [Local pigment stimulation by alpha-melanocyte stimulating hormone in the human: intracutaneous injections without and with ultraviolet irradiation]
Z Hautkr. 1989 Jun 15;64(6):459-60. German.




Spiro J, Parker S, Oliver I, Fraser C, Marks JM, Thody AJ. Effect of PUVA on plasma and skin immunoreactive alpha-melanocyte stimulating hormone concentrations.
Br J Dermatol. 1987 Dec;117(6):703-7.


Nordlund JJ, Collins CE, Rheins LA. Prostaglandin E2 and D2 but not MSH stimulate the proliferation of pigment cells in the pinnal epidermis of the DBA/2 mouse.
J Invest Dermatol. 1986 Apr;86(4):433-7.


Altmeyer P, Stohr L, Holzmann H. Seasonal rhythm of the plasma level of alpha-melanocyte stimulating hormone.
J Invest Dermatol. 1986 Apr;86(4):454-6.


Bartelt RN, Altmeyer P, Stohr L, Holzmann H. [Endocrinological reactions following UV A whole body irradiation]
Derm Beruf Umwelt. 1985;33(2):50-5. German.


Bartelt RN, Altmeyer P, Stohr L, Chilf GN, Holzmann H. [Effect of ultraviolet rays on alpha-MSH plasma concentration]
Z Hautkr. 1984 Aug 15;59(16):1053-5. German.


Holzmann H, Altmeyer P, Stohr L, Chilf GN. [Modification of alpha-MSH by UVA irradiation of the skin]
Hautarzt. 1983 Jun;34(6):294-7. German.


Parker F. The biology of pigmentation.
Birth Defects Orig Artic Ser. 1981;17(2):79-91. Review.