15-deoxy-delta12,14-prostaglandin-J2 inhibits expression of eNOS in human endothelial cells.
15-Deoxy-delta12,14-Prostaglandin-J2 (15d-PGJ2), an endogenous ligand of PPARgamma transcription factor, modifies expression of many genes involved in inflammation and angiogenesis. Enzyme which contributes to regulation of both these processes is endothelial nitric oxide synthase (eNOS). Our aim was to investigated the effect of 15d-PGJ2 on eNOS in human umbilical vein endothelial cells (HUVEC). We demonstrated that 24 h incubation of HUVEC with 15d-PGJ2 (1-10 microM) does not influence eNOS. On the contrary, the longer exposure (48-72 h) resulted in concentration-dependent inhibition of eNOS mRNA and protein expressions and led to reduction in eNOS enzymatic activity by approximately 50%. This effect was mediated by regulation of the transcription rate from eNOS promoter, what may be associated with inhibition of AP-1 binding capacity. The stability of mRNA was unchanged. Since none of the observed effects could be mimicked by troglitazone, a more potent PPARgamma ligand, we suppose that 15d-PGJ2 diminishes expression of eNOS via PPARgamma-independent mechanisms.
Józkowicz
Alicja
A
Faculty of Biotechnology, Jagiellonian University, Gronostajowa 7, Krakow 30-387, Poland. alicia@mol.uj.edu.pl
Nigisch
Anneliese
A
Winter
Birgitta
B
Weigel
Guenter
G
Hukb
Ihor
I
Dulaka
Józef
J
D001483:Base Sequence; D002460:Cell Line; D017931:DNA Primers; D024202:Electrophoretic Mobility Shift Assay; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000235:genetics; D052250:Nitric Oxide Synthase Type III; D047495:PPAR gamma / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D015230:Prostaglandin D2 / Q000031:analogs & derivatives* / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D018808:Transcription Factor AP-1 / Q000378:metabolism
C097240:15-deoxy-delta(12,14)-prostaglandin J2; D017931:DNA Primers; D047495:PPAR gamma; D012333:RNA, Messenger; D018808:Transcription Factor AP-1; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; D015230:Prostaglandin D2