High-affinity binding and lack of growth-promoting activity of 12(S)-hydroxyeicosatetraenoic acid (12(S)-HETE) in a human epidermal cell line.
The arachidonic acid metabolite 12-hydroxyeicosatetraenoic acid (12-HETE) is assumed to play an important role in skin physiology and pathophysiology. Specifically, it has recently been discussed as a growth promoting agent in keratinocytes. Our aim was to find out whether epidermal cells possess specific receptors for 12-HETE which would mediate the effects of this eicosanoid in skin, including the putative growth stimulating activity. We could identify specific binding sites for 12(S)-HETE on the human epidermal cell line SCL-II. The analysis of binding data revealed a single class of binding sites with a Kd of 2,6 nM and a Bmax of 216,000 sites per cell. The binding was saturable, readily reversible, and specific for 12(S)-HETE with lower affinities for other monoHETE. We failed to detect any significant proliferative activity of 12(S)-HETE in the same epidermal cell line, although we applied three independent methods for evaluation of cell growth and used a concentration of 12(S)-HETE which should enable an optimal receptor occupancy. Thus, epidermal cells possess high-affinity 12(S)-HETE binding sites which are likely to be involved in the effects of this eicosanoid in epidermis. However, biologic effects other than direct growth stimulation seem to be transduced by 12(S)-HETE receptors in epidermal cells which need further investigation.
Gross
E
E
Department of Dermatology, University of Munich, Federal Republic of Germany.
Ruzicka
T
T
von Restorff
B
B
Stolz
W
W
Klotz
K N
KN
D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D001665:Binding Sites / Q000502:physiology*; D002294:Carcinoma, Squamous Cell / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004247:DNA / Q000032:analysis; D006128:Growth / Q000502:physiology; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000378:metabolism*; D011955:Receptors, Drug / Q000502:physiology*; D012867:Skin / Q000648:ultrastructure*; D014407:Tumor Cells, Cultured
D006893:Hydroxyeicosatetraenoic Acids; D011955:Receptors, Drug; D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D004247:DNA