Interest in colorless intermediates of melanocyte metab. has traditionally been related to their role as melanin precursors, though several lines of evidence scattered in the literature suggested that these compds. may exert an antioxidant and protective function per se unrelated to pigment synthesis. Herein, we disclose the remarkable protective and differentiating effects of 5,6-dihydroxyindole-2-carboxylic acid (DHICA), a diffusible dopachrome tautomerase (DCT)-dependent eumelanin intermediate, on primary cultures of human keratinocytes. At micromolar concns., DHICA induced: (a) time- and dose-dependent redn. of cell proliferation without concomitant toxicity; (b) enhanced expression of early (spinous keratins K1 and K10 and envelope protein involucrin) and late (loricrin and filaggrin) differentiation markers; (c) increased activities and expression of antioxidant enzymes; and (d) decreased cell damage and apoptosis following UVA exposure. The hitherto unrecognized role of DHICA as an antiproliferative, protective, and antiapoptotic endogenous cell messenger points to a reappraisal of the biol. functions of melanocytes and DCT in skin homeostasis and photoprotection beyond the mere provision of melanin pigments, and provides, to our knowledge, a previously unreported possible explanation to the higher resistance of the dark-skinned eumelanic phenotypes to sunburn and skin cancer.

The Eumelanin Intermediate 5,6-Dihydroxyindole-2-Carboxylic Acid Is a Messenger in the Cross-Talk among Epidermal Cells / Kovacs, D.; Flori, E.; Maresca, V.; Ottaviani, M.; Aspite, N.; Dell'Anna, M. L.; Panzella, Lucia; Napolitano, Alessandra; Picardo, M.; D'Ischia, Marco. - In: JOURNAL OF INVESTIGATIVE DERMATOLOGY. - ISSN 0022-202X. - 132:4(2012), pp. 1196-1205. [10.1038/jid.2011.457]

The Eumelanin Intermediate 5,6-Dihydroxyindole-2-Carboxylic Acid Is a Messenger in the Cross-Talk among Epidermal Cells

PANZELLA, LUCIA;NAPOLITANO, ALESSANDRA;D'ISCHIA, MARCO
2012

Abstract

Interest in colorless intermediates of melanocyte metab. has traditionally been related to their role as melanin precursors, though several lines of evidence scattered in the literature suggested that these compds. may exert an antioxidant and protective function per se unrelated to pigment synthesis. Herein, we disclose the remarkable protective and differentiating effects of 5,6-dihydroxyindole-2-carboxylic acid (DHICA), a diffusible dopachrome tautomerase (DCT)-dependent eumelanin intermediate, on primary cultures of human keratinocytes. At micromolar concns., DHICA induced: (a) time- and dose-dependent redn. of cell proliferation without concomitant toxicity; (b) enhanced expression of early (spinous keratins K1 and K10 and envelope protein involucrin) and late (loricrin and filaggrin) differentiation markers; (c) increased activities and expression of antioxidant enzymes; and (d) decreased cell damage and apoptosis following UVA exposure. The hitherto unrecognized role of DHICA as an antiproliferative, protective, and antiapoptotic endogenous cell messenger points to a reappraisal of the biol. functions of melanocytes and DCT in skin homeostasis and photoprotection beyond the mere provision of melanin pigments, and provides, to our knowledge, a previously unreported possible explanation to the higher resistance of the dark-skinned eumelanic phenotypes to sunburn and skin cancer.
2012
The Eumelanin Intermediate 5,6-Dihydroxyindole-2-Carboxylic Acid Is a Messenger in the Cross-Talk among Epidermal Cells / Kovacs, D.; Flori, E.; Maresca, V.; Ottaviani, M.; Aspite, N.; Dell'Anna, M. L.; Panzella, Lucia; Napolitano, Alessandra; Picardo, M.; D'Ischia, Marco. - In: JOURNAL OF INVESTIGATIVE DERMATOLOGY. - ISSN 0022-202X. - 132:4(2012), pp. 1196-1205. [10.1038/jid.2011.457]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/457858
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