Upregulation of the Human Alkaline Ceramidase 1 and Acid Ceramidase Mediates Calcium-Induced Differentiation of Epidermal Keratinocytes

Upregulation of the Human Alkaline Ceramidase 1 and Acid Ceramidase Mediates Calcium-Induced Differentiation of Epidermal Keratinocytes

Extracellular calcium (Cao2+) potently induces the growth arrest and differentiation of human epidermal keratinocytes (HEKs). We report that Cao2+ markedly upregulates the human alkaline ceramidase 1 (haCER1) in HEKs; and its upregulation mediates the Cao2+-induced growth arrest and differentiation...

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Bibliographic Details
Published in:Journal of investigative dermatology Vol. 128; no. 2; pp. 389 - 397
Main Authors: Sun, Wei, Xu, Ruijuan, Hu, Wei, Jin, Junfei, Crellin, Heather A., Bielawski, Jacek, Szulc, Zdzislaw M., Thiers, Bruce H., Obeid, Lina M., Mao, Cungui
Format: Journal Article
Language:English
Published: Danvers, MA Elsevier Inc 01-02-2008
Nature Publishing
Elsevier Limited
Subjects:
Acid Ceramidase
Alkaline Ceramidase
Amidohydrolases - genetics
Amidohydrolases - metabolism
Biological and medical sciences
Calcium - metabolism
Calcium - pharmacology
Cell Differentiation - physiology
Cell Division - physiology
Cells, Cultured
Ceramidases
Ceramides - metabolism
Dermatology
Endoplasmic Reticulum - enzymology
Epidermal Growth Factor - metabolism
Epidermal Growth Factor - pharmacology
Epidermis - cytology
Fatty Acids, Unsaturated - metabolism
Galactosylgalactosylglucosylceramidase - genetics
Galactosylgalactosylglucosylceramidase - metabolism
Gene Expression Regulation, Enzymologic
Humans
Keratinocytes - cytology
Keratinocytes - enzymology
Medical sciences
RNA, Small Interfering
Substrate Specificity
Up-Regulation - physiology
Human
Calcium
Enzyme
Dermatology
Hydrolases
Epidermis
Keratinocyte
Cell differentiation
Differentiation
Inorganic element
Ceramidase
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Summary:Extracellular calcium (Cao2+) potently induces the growth arrest and differentiation of human epidermal keratinocytes (HEKs). We report that Cao2+ markedly upregulates the human alkaline ceramidase 1 (haCER1) in HEKs; and its upregulation mediates the Cao2+-induced growth arrest and differentiation of HEKs. haCER1 is the human ortholog of mouse alkaline ceramidase 1 that we previously identified. haCER1 catalyzed the hydrolysis of very long-chain ceramides to generate sphingosine (SPH). This in vitro activity required Ca2+. Ectopic expression of haCER1 in HEKs decreased the levels of D-e-C24:1-ceramide and D-e-C24:0-ceramide but elevated the levels of both SPH and its phosphate (S1P), whereas RNA interference-mediated knockdown of haCER1 caused the opposite effects on the levels of these sphingolipids in HEKs. Similar to haCER1 overexpression, Cao2+ increased the levels of SPH and S1P, and this was attenuated by haCER1 knockdown. haCER1 knockdown also inhibited the Cao2+-induced growth arrest of HEKs and the Cao2+-induced expression of keratin 1 and involucrin in HEKs. In addition, the acid ceramidase (AC) was also upregulated by Cao2+; and its knockdown attenuated the Cao2+-induced expression of keratin 1 and involucrin in HEKs. These results strongly suggest that upregulation of haCER1 and AC mediates the Cao2+-induced growth arrest and differentiation of HEKs by generating SPH and S1P.
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ISSN:0022-202X
1523-1747
DOI:10.1038/sj.jid.5701025