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Calcium‐mediated regulation of the low density lipoprotein receptor and intracellular cholesterol synthesis in human epidermal keratinocytes
Author(s) -
Ponec Maria,
Havekes Louis,
Kempenaar Johanna,
Lavrijsen Sjan,
Wijsman Marian,
Boonstra Johannes,
Vermeer Bert Jan
Publication year - 1985
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.1041250113
Subject(s) - calcium , extracellular , cholesterol , calcium in biology , ldl receptor , lipoprotein , low density lipoprotein , chemistry , endocrinology , medicine , intracellular , cell culture , keratinocyte , biochemistry , biology , microbiology and biotechnology , in vitro , genetics
Unlike cells cultured under physiological Ca 2+ concentrations (1–2 mM), keratinocytes cultured in media containing Ca 2+ in low concentrations (less than 0.1 mM) do not stratify. The latter cells also differ with respect to several features of the regulation of cholesterol synthesis. In keratinocytes cultured in medium containing high Ca 2+ concentrations (1.6 mM) and fetal calf serum, the rate of cholesterol synthesis was 20–30 times higher than in keratinocytes exposed to a low Ca 2+ concentration. The rate of cholesterol synthesis did not change when high‐calcium cells were deprived of extracellular sources of cholesterol but increased (8–10 fold) in deprived low‐calcium cells. Furthermore, the addition of low density lipoprotein (LDL) reduced cholesterol synthesis markedly in low‐calcium cells but had no effect on high‐calcium cells. Finally, in keratinocytes cultured at low calcium concentrations the association and degradation of 125 I‐LDL was 20–30 times higher than in keratinocytes cultured under high‐calcium conditions. Switching of the cells from the low‐calcium to the high‐calcium medium resulted in the induction of terminal differentiation within 15 hours and was accompanied by increased cholesterol and protein synthesis, increased competence of cells to form cornified envelopes, and reduced association of 125 I‐LDL. A gradual increase of the extracellular Ca 2+ concentration was accompanied by a corresponding increase of cholesterol and protein synthesis and a decrease of the response of intracellular cholesterol synthesis to changes in the extracellular concentrations of lipoprotein. Various morphological techniques showed virtually no binding and internalization of LDL by keratinocytes cultured at the high‐calcium level, whereas both were observed at the low‐calcium level. Once internalized, the LDL was delivered to dense bodies representing lysosomes. It is concluded that in human epidermal keratinocytes, the expression of the LDL receptor and the endogenous synthesis of cholesterol are regulated by the conditions determined by the differentiation stage of the cells.