Differentiation of human keratinocytes: changes in lipid synthesis, plasma membrane lipid composition, and /sup 125/I-EGF binding upon administration of 25-hydroxycholesterol and mevinolin
We have studied the relationship between differentiation capacity, plasma membrane composition, and epidermal growth factor (EGF) receptor expression of normal keratinocytes in vitro. The plasma membrane composition of the cells was modulated experimentally by cholesterol depletion, using specific inhibitors of cholesterol synthesis, such as 25-hydroxycholesterol and mevinolin. Exposure of the cells towards these inhibitors resulted in a drastic decrease of cholesterol biosynthesis, as determined from /sup 14/C-acetate incorporation into the various lipid fractions. This effect on cholesterol biosynthesis was reflected by changes in plasma membrane composition, as determined by lipid analysis of isolated plasma membrane fractions, these resulting in a decreased cholesterol-phospholipid ratio. The experimental modulation of plasma membrane composition by 25-hydroxycholesterol or mevinolin were accompanied by a decreased cornified envelope formation and by high expression of EGF binding sites. These phenomena were more pronounced in cells induced to differentiate by exposure of cells grown under low Ca2+ to normal Ca2+ concentrations, as compared to cells grown persistently under low Ca2+ concentrations. These results suggest a close correlation between plasma membrane composition, differentiation capacity, and EGF receptor expression.
- Research Organization:
- Univ. Hospital, Leiden, The Netherlands
- OSTI ID:
- 5607747
- Journal Information:
- J. Cell. Physiol.; (United States), Journal Name: J. Cell. Physiol.; (United States) Vol. 133:2; ISSN JCLLA
- Country of Publication:
- United States
- Language:
- English
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59 BASIC BIOLOGICAL SCIENCES
ALKALINE EARTH METAL COMPOUNDS
ANIMAL CELLS
ANIMAL TISSUES
BETA DECAY RADIOISOTOPES
BIOCHEMICAL REACTION KINETICS
BIOSYNTHESIS
BODY
CALCIUM COMPOUNDS
CARBON 14 COMPOUNDS
CELL CONSTITUENTS
CELL DIFFERENTIATION
CELL MEMBRANES
CHOLESTEROL
DAYS LIVING RADIOISOTOPES
ELECTRON CAPTURE RADIOISOTOPES
EPIDERMIS
EPITHELIUM
GROWTH FACTORS
HYDROXY COMPOUNDS
INTERMEDIATE MASS NUCLEI
IODINE 125
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
KERATIN
KINETICS
LABELLED COMPOUNDS
LIPIDS
MEMBRANE PROTEINS
MEMBRANES
MITOGENS
NUCLEI
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
ORGANS
PROTEINS
RADIOISOTOPES
REACTION KINETICS
RECEPTORS
SCLEROPROTEINS
SKIN
STEROIDS
STEROLS
SYNTHESIS
TISSUES
TRACER TECHNIQUES