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Sphingosine 1-phosphate protects primary human keratinocytes from apoptosis via nitric oxide formation through the receptor subtype S1P(3)

  • Although the lipid mediator sphingosine 1-phosphate (S1P) has been identified to induce cell growth arrest of human keratinocytes, the sphingolipid effectively protects these epidermal cells from apoptosis. The molecular mechanism of the anti-apoptotic action induced by S1P is less characterized. Apart from S1P, endogenously produced nitric oxide (NOaEuro cent) has been recognized as a potent modulator of apoptosis in keratinocytes. Therefore, it was of great interest to elucidate whether S1P protects human keratinocytes via a NOaEuro cent-dependent signalling pathway. Indeed, S1P induced an activation of endothelial nitric oxide synthase (eNOS) in human keratinocytes leading to an enhanced formation of NOaEuro cent. Most interestingly, the cell protective effect of S1P was almost completely abolished in the presence of the eNOS inhibitor L-NAME as well as in eNOS-deficient keratinocytes indicating that the sphingolipid metabolite S1P protects human keratinocytes from apoptosis via eNOS activation and subsequent production ofAlthough the lipid mediator sphingosine 1-phosphate (S1P) has been identified to induce cell growth arrest of human keratinocytes, the sphingolipid effectively protects these epidermal cells from apoptosis. The molecular mechanism of the anti-apoptotic action induced by S1P is less characterized. Apart from S1P, endogenously produced nitric oxide (NOaEuro cent) has been recognized as a potent modulator of apoptosis in keratinocytes. Therefore, it was of great interest to elucidate whether S1P protects human keratinocytes via a NOaEuro cent-dependent signalling pathway. Indeed, S1P induced an activation of endothelial nitric oxide synthase (eNOS) in human keratinocytes leading to an enhanced formation of NOaEuro cent. Most interestingly, the cell protective effect of S1P was almost completely abolished in the presence of the eNOS inhibitor L-NAME as well as in eNOS-deficient keratinocytes indicating that the sphingolipid metabolite S1P protects human keratinocytes from apoptosis via eNOS activation and subsequent production of protective amounts of NOaEuro cent. It is well established that most of the known actions of S1P are mediated by a family of five specific G protein-coupled receptors. Therefore, the involvement of S1P-receptor subtypes in S1P-mediated eNOS activation has been examined. Indeed, this study clearly shows that the S1P(3) is the exclusive receptor subtype in human keratinocytes which mediates eNOS activation and NOaEuro cent formation in response to S1P. In congruence, when the S1P(3) receptor subtype is abrogated, S1P almost completely lost its ability to protect human keratinocytes from apoptosis.show moreshow less

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Metadaten
Author:Elisabeth I. Schmitz, Henrik Potteck, Melanie Schüppel, Marianti Manggau, Elly Wahydin, Burkhard KleuserORCiDGND
DOI:https://doi.org/10.1007/s11010-012-1433-5
ISSN:0300-8177 (print)
Parent Title (English):Molecular and cellular biochemistry : an international journal for chemical biology in health and disease
Publisher:Springer
Place of publication:Dordrecht
Document Type:Article
Language:English
Year of first Publication:2012
Year of Completion:2012
Release Date:2017/03/26
Tag:Apoptosis; Endothelial nitric oxide synthase; Keratinocytes; Nitric oxide; S1P-receptors; Sphingolipids; Sphingosine 1-phosphate
Volume:371
Issue:1-2
Pagenumber:12
First Page:165
Last Page:176
Funder:Deutsche Forschungsgemeinschaft [Kl 988 7-1]
Organizational units:Philosophische Fakultät / Institut für Germanistik
Peer Review:Referiert