PMID- 14708615
OWN - NLM
STAT- MEDLINE
DCOM- 20040122
LR  - 20151119
IS  - 0022-202X (Print)
IS  - 0022-202X (Linking)
VI  - 121
IP  - 5
DP  - 2003 Nov
TI  - Differential regulation of cyclooxygenase-2 expression by phytosphingosine 
      derivatives, NAPS and TAPS, and its role in the NAPS or TAPS-mediated apoptosis.
PG  - 1126-34
AB  - We investigated the effect of novel phytosphingosine derivatives, N-acetyl 
      phytosphingosine (NAPS) and tetra-acetyl phytosphingosine (TAPS), on induction of 
      apoptosis in HaCaT cells in comparison with C2-ceramide. NAPS/TAPS effectively 
      decreased cell viability in a dose dependent manner mainly due to apoptosis. An 
      apoptosis expression array analysis showed that in the TAPS treated cells 13 
      genes including COX-2 encoding cyclooxygenase-2, the most induced by TAPS, were 
      up-regulated while 23 others down-regulated. Therefore, we examined the mechanism 
      underlying the altered expression of COX-2. Assays with inhibitors and antibodies 
      against proteins involved in signal transduction demonstrated that NAPS and TAPS 
      elevated COX-2 expression via tyrosine kinase, src, PI-3 kinase and PKC, followed 
      by ERK activation. However, P38 was not involved in the NAPS-mediated COX-2 
      expression but in the TAPS-mediated. We further demonstrated by FACS analyses 
      that NAPS- or TAPS-mediated apoptosis was greatly increased in cells treated with 
      celecoxib, a selective COX-2 inhibitor. Inhibition of the ERK pathway apparently 
      involved in the NAPS/TAPS-mediated COX-2 expression enhanced the 
      NAPS/TAPS-mediated apoptosis, whereas inhibition of the P38 pathway did not. 
      These results suggest that expression of COX-2 in the TAPS- or NAPS-treated cells 
      may be increased to counteract the effect of those compounds on apoptosis.
FAU - Kim, Hye Jung
AU  - Kim HJ
AD  - Department of Dermato-Immunology, The Catholic University of Korea, Seoul, South 
      Korea.
FAU - Shin, Weonhye
AU  - Shin W
FAU - Park, Chang Seo
AU  - Park CS
FAU - Kim, Hyung-Ok
AU  - Kim HO
FAU - Kim, Tae-Yoon
AU  - Kim TY
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Invest Dermatol
JT  - The Journal of investigative dermatology
JID - 0426720
RN  - 0 (Isoenzymes)
RN  - 0 (Membrane Proteins)
RN  - EC 1.14.99.1 (Cyclooxygenase 2)
RN  - EC 1.14.99.1 (PTGS2 protein, human)
RN  - EC 1.14.99.1 (Prostaglandin-Endoperoxide Synthases)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.10.2 (src-Family Kinases)
RN  - EC 2.7.11.13 (Protein Kinase C)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
RN  - GIN46U9Q2Q (phytosphingosine)
RN  - NGZ37HRE42 (Sphingosine)
SB  - IM
MH  - Apoptosis/*drug effects
MH  - Cell Line
MH  - Cell Survival/drug effects
MH  - Cyclooxygenase 2
MH  - Dose-Response Relationship, Drug
MH  - Gene Expression Regulation/drug effects
MH  - Humans
MH  - Isoenzymes/antagonists & inhibitors/*biosynthesis
MH  - Membrane Proteins
MH  - Mitogen-Activated Protein Kinase 1/physiology
MH  - Mitogen-Activated Protein Kinases/physiology
MH  - Phosphatidylinositol 3-Kinases/physiology
MH  - Prostaglandin-Endoperoxide Synthases/*biosynthesis
MH  - Protein Kinase C/physiology
MH  - Sphingosine/*analogs & derivatives/*pharmacology
MH  - p38 Mitogen-Activated Protein Kinases
MH  - src-Family Kinases/physiology
EDAT- 2004/01/08 05:00
MHDA- 2004/01/24 05:00
CRDT- 2004/01/08 05:00
PHST- 2004/01/08 05:00 [pubmed]
PHST- 2004/01/24 05:00 [medline]
PHST- 2004/01/08 05:00 [entrez]
AID - S0022-202X(15)30472-3 [pii]
AID - 10.1046/j.1523-1747.2003.12554.x [doi]
PST - ppublish
SO  - J Invest Dermatol. 2003 Nov;121(5):1126-34. doi: 
      10.1046/j.1523-1747.2003.12554.x.