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Vitamin A esterification in human epidermis: a relation to keratinocyte differentiation
1Department of Dermatology, University of Linköping, Sweden.
The Journal of Investigative Dermatology
|January 1, 1990
Summary
Epidermal cells contain retinol and its esters, with higher concentrations in outer layers. Vitamin A esterification by acyl CoA:retinol acyltransferase (ARAT) may be crucial for keratinocyte differentiation and is reduced in skin cancers.
Area of Science:
- Biochemistry
- Dermatology
- Cell Biology
Background:
- Vitamin A, including retinol and 3,4-didehydroretinol, is present in epidermal keratinocytes.
- Retinol and its derivatives exist in both unesterified and fatty acyl ester forms within the epidermis.
Purpose of the Study:
- To investigate the distribution and synthesis of vitamin A congeners and their esters in different epidermal layers.
- To characterize the enzyme responsible for vitamin A esterification, acyl CoA:retinol acyltransferase (ARAT), in human skin.
- To explore the role of vitamin A esterification in keratinocyte differentiation and its alterations in skin cancers.
Main Methods:
- High-performance liquid chromatography (HPLC) to quantify retinol, 3,4-didehydroretinol, and their esters in epidermal layers.
- Organ culture of human breast skin with [3H]retinol to study in situ synthesis of vitamin A esters.
- Subcellular fractionation and enzyme assays to determine ARAT activity and its pH optimum.
- Comparison of ARAT activity and retinyl ester levels in normal epidermis, basal cell carcinoma, and squamous cell carcinoma.
Main Results:
- Concentrations of unesterified vitamin A congeners and their fatty acyl esters increase from inner to outer epidermal layers.
- Fatty acyl esters constitute a significant portion of total vitamin A, especially in the stratum granulosum/corneum (71%).
- In situ synthesis studies confirmed retinyl esters as the most abundant radioactive compounds in the epidermis after retinol incubation.
- ARAT activity was highest in the microsomal fraction, with a pH optimum of 5.5-6.0.
- ARAT activity was significantly reduced in basal cell carcinomas and squamous cell carcinomas compared to normal epidermis.
Conclusions:
- Vitamin A esterification by ARAT is a key process in terminally differentiating keratinocytes, potentially influenced by epidermal pH gradients.
- Reduced ARAT activity and lower retinyl ester levels in skin cancers suggest a role for vitamin A esterification in preventing or modulating abnormal keratinocyte proliferation.