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Lanthanum influx into cultured human keratinocytes: Effect on calcium flux and terminal differentiation
Author(s) -
Pillai Sreekumar,
Bikle Daniel D.
Publication year - 1992
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.1041510323
Subject(s) - ionomycin , calcium , extracellular , keratinocyte , chemistry , ionophore , biophysics , intracellular , calcium in biology , biochemistry , microbiology and biotechnology , in vitro , biology , organic chemistry
Trivalent cation lanthanum (La) binds to calcium binding sites of cells and either mimics the properties of calcium or inhibits the effects of calcium by displacing calcium from its binding sites. Extracellular calcium induces differentiation of human epidermal keratinocytes in culture, in part by increasing the intracellular calcium levels (Ca i ). Therefore, in this study we determined the effect of La on differentiation and intracellular calcium levels of keratinocytes. We observed that La inhibited the production of cornified envelopes, a marker for terminal differentiation of keratinocytes. La inhibited the calcium requiring envelope cross‐linking enzyme, transglutaminase, in a direct manner, presumably, by displacing calcium from its binding site on the enzyme. La inhibited the influx and the efflux of 45 Ca from keratinocytes. Paradoxically, extracellular La appeared to increase the Ca i levels of keratinocytes as measured by the fluorescent probe indo‐1. However, subsequent experiments revealed that indo‐1 bound La with a higher affinity than Ca and emitted fluorescence in the same wavelength as the Ca bound form. Using this probe, we observed that La enters keratinocytes in a dose‐dependent fashion and achieves concentrations exceeding 80 nM when the external La concentration is raised to 300 μM. This fully accounted for the apparent increase in Ca i when La was added to the cells. Treatment of cells with ionomycin increased indo‐1 fluorescence maximally in the presence of La indicating influx of La via this Ca specific ionophore. Our results indicate that La enters cells and inhibits calcium mediated keratinocyte differentiation both by blocking Ca influx and by blocking calcium regulated intracellular processes such as transglutaminase directed cornified envelope formation. © 1992 Wiley‐Liss, Inc.