Extracellular ATP and ADP activate transcription factor NF-kappa B and induce endothelial cell apoptosis.
Inflammation within the vasculature is associated with endothelial cell (EC) perturbation, loss of vascular ATP-diphosphohydrolase activity, and platelet microthrombus formation with release of ATP and ADP into the micro-environment. The nature and effects of purinergic stimulation of EC under these circumstances remain largely undetermined. ATP and ADP activated EC transcribed mRNA from certain transcription factor NF-kappa B target genes and expressed E-selectin protein on cell membranes. Band shift analysis and reporter assays confirmed the activation of NF-kappa B in response to both ATP and ADP. Apoptosis was shown to occur in response to purinergic signaling, potentially through the activation of P2z/P2x7 receptors. Induction of EC activation responses and apoptosis in response to stimulation with ATP and ADP is associated with activation of NF-kappa B.
Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA.
M
M
von Albertini
A
A
Palmetshofer
E
E
Kaczmarek
K
K
Koziak
D
D
Stroka
S T
ST
Grey
K M
KM
Stuhlmeier
S C
SC
Robson
D000244:Adenosine Diphosphate / Q000494:pharmacology*; D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D001011:Aorta; D017209:Apoptosis / Q000187:drug effects*; D002417:Cattle; D002478:Cells, Cultured; D019040:E-Selectin / Q000096:biosynthesis*; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D017930:Genes, Reporter; D016297:Mutagenesis, Site-Directed; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis; D011983:Receptors, Purinergic / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000378:metabolism; D013552:Swine; D051841:Transcription Factor RelB; D014157:Transcription Factors; D014158:Transcription, Genetic / Q000187:drug effects / Q000502:physiology*; D014162:Transfection
D019040:E-Selectin; D016328:NF-kappa B; D011518:Proto-Oncogene Proteins; D011983:Receptors, Purinergic; D011994:Recombinant Proteins; D014157:Transcription Factors; D051841:Transcription Factor RelB; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate