PMID- 22297637
OWN - NLM
STAT- MEDLINE
DCOM- 20120521
LR  - 20211203
IS  - 1523-1747 (Electronic)
IS  - 0022-202X (Linking)
VI  - 132
IP  - 4
DP  - 2012 Apr
TI  - The eumelanin intermediate 5,6-dihydroxyindole-2-carboxylic acid is a messenger 
      in the cross-talk among epidermal cells.
PG  - 1196-205
LID - 10.1038/jid.2011.457 [doi]
AB  - Interest in colorless intermediates of melanocyte metabolism has traditionally 
      been related to their role as melanin precursors, though several lines of 
      evidence scattered in the literature suggested that these compounds 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 concentrations, DHICA induced: (a) time- and 
      dose-dependent reduction 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 biological 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.
FAU - Kovacs, Daniela
AU  - Kovacs D
AD  - Laboratory of Cutaneous Physiopathology and Integrated Center of Metabolomics 
      Research, San Gallicano Dermatologic Institute (IRCCS), Rome, Italy.
FAU - Flori, Enrica
AU  - Flori E
FAU - Maresca, Vittoria
AU  - Maresca V
FAU - Ottaviani, Monica
AU  - Ottaviani M
FAU - Aspite, Nicaela
AU  - Aspite N
FAU - Dell'Anna, Maria Lucia
AU  - Dell'Anna ML
FAU - Panzella, Lucia
AU  - Panzella L
FAU - Napolitano, Alessandra
AU  - Napolitano A
FAU - Picardo, Mauro
AU  - Picardo M
FAU - d'Ischia, Marco
AU  - d'Ischia M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120202
PL  - United States
TA  - J Invest Dermatol
JT  - The Journal of investigative dermatology
JID - 0426720
RN  - 0 (FLG protein, human)
RN  - 0 (Filaggrin Proteins)
RN  - 0 (Indoles)
RN  - 0 (Intermediate Filament Proteins)
RN  - 0 (Melanins)
RN  - 0 (Membrane Proteins)
RN  - 0 (Peroxisome Proliferator-Activated Receptors)
RN  - 0 (Protein Precursors)
RN  - 0 (loricrin)
RN  - 12627-86-0 (eumelanin)
RN  - 4790-08-3 (5,6-dihydroxy-2-indolylcarboxylic acid)
RN  - 60108-77-2 (involucrin)
RN  - 68238-35-7 (Keratins)
SB  - IM
MH  - Apoptosis/drug effects/radiation effects
MH  - Cell Communication/*drug effects/physiology
MH  - Cell Differentiation/*drug effects
MH  - Cell Proliferation/*drug effects
MH  - Cells, Cultured
MH  - Dose-Response Relationship, Drug
MH  - *Epidermal Cells
MH  - Epidermis/*drug effects/metabolism
MH  - Filaggrin Proteins
MH  - Humans
MH  - Indoles/*pharmacology
MH  - Intermediate Filament Proteins/metabolism
MH  - Keratinocytes/cytology/drug effects/metabolism
MH  - Keratins/metabolism
MH  - Melanins/*metabolism
MH  - Melanocytes/cytology/drug effects/metabolism
MH  - Membrane Proteins/metabolism
MH  - Peroxisome Proliferator-Activated Receptors/metabolism
MH  - Protein Precursors/metabolism
MH  - Time Factors
EDAT- 2012/02/03 06:00
MHDA- 2012/05/23 06:00
CRDT- 2012/02/03 06:00
PHST- 2012/02/03 06:00 [entrez]
PHST- 2012/02/03 06:00 [pubmed]
PHST- 2012/05/23 06:00 [medline]
AID - S0022-202X(15)35694-3 [pii]
AID - 10.1038/jid.2011.457 [doi]
PST - ppublish
SO  - J Invest Dermatol. 2012 Apr;132(4):1196-205. doi: 10.1038/jid.2011.457. Epub 2012 
      Feb 2.