Abstract |
Aldehyde dehydrogenase 1A1 (ALDH1A1), an enzyme that catalyses the conversion of lipid aldehydes to lipid carboxylic acids, plays pleiotropic roles in UV-radiation resistance, melanogenesis and stem cell maintenance. In this study, a combination of RNAi and pharmacologic approaches were used to determine which ALDH1A1 substrates and products regulate melanogenesis. Initial studies revealed that neither the UV-induced lipid aldehyde 4-hydroxy-2-nonenal nor the ALDH1A1 product all-trans retinoic acid appreciably induced melanogenesis. In contrast, both the ALDH1A1 substrate 9-cis retinal and its corresponding product 9-cis retinoic acid potently induced the accumulation of MITF mRNA, Tyrosinase mRNA and melanin. ALDH1A1 depletion inhibited the ability of 9-cis retinal but not 9-cis retinoic acid to stimulate melanogenesis, indicating that ALDH1A1 regulates melanogenesis by catalysing the conversion of 9-cis retinal to 9-cis retinoic acid. The addition of potent ALDH1A inhibitors ( cyanamide or Angeli's salt) suppressed Tyrosinase and MITF mRNA accumulation in vitro and also melanin accumulation in skin equivalents, suggesting that 9-cis retinoids regulate melanogenesis in the intact epidermis. Taken together, these studies not only identify cyanamide as a potential novel treatment for hyperpigmentary disorders, but also identify 9-cis retinoic acid as a pigment stimulatory agent that may have clinical utility in the treatment of hypopigmentary disorders, such as vitiligo.
|
Authors | Elyse K Paterson, Hsiang Ho, Rubina Kapadia, Anand K Ganesan |
Journal | Experimental dermatology
(Exp Dermatol)
Vol. 22
Issue 3
Pg. 202-9
(Mar 2013)
ISSN: 1600-0625 [Electronic] Denmark |
PMID | 23489423
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
|
Copyright | © 2013 John Wiley & Sons A/S. |
Chemical References |
- MITF protein, human
- Melanins
- Microphthalmia-Associated Transcription Factor
- Alitretinoin
- Cyanamide
- Tretinoin
- Monophenol Monooxygenase
- Aldehyde Dehydrogenase 1 Family
- Aldehyde Dehydrogenase
- ALDH1A1 protein, human
- Retinal Dehydrogenase
|
Topics |
- Aldehyde Dehydrogenase
(metabolism)
- Aldehyde Dehydrogenase 1 Family
- Alitretinoin
- Cell Line, Tumor
- Cells, Cultured
- Cyanamide
(pharmacology)
- Humans
- Melanins
(metabolism)
- Melanocytes
(drug effects, metabolism, pathology)
- Melanoma
(metabolism, pathology)
- Microphthalmia-Associated Transcription Factor
(metabolism)
- Monophenol Monooxygenase
(metabolism)
- Retinal Dehydrogenase
- Skin
(drug effects, metabolism, pathology)
- Skin Neoplasms
(metabolism, pathology)
- Skin Pigmentation
(physiology)
- Tretinoin
(metabolism, pharmacology)
|