A paradoxical pro-apoptotic effect of thrombin on smooth muscle cells.
Whereas thrombin (below 10 nM) is a potent mitogen, recent studies report that exposure to higher doses of thrombin could lead to apoptosis of neurons and tumor cells. Our results show that prolonged exposure (> or = 24 h) to thrombin (50-100 nM) exerts a pro-apoptotic effect on cultured vascular smooth muscle cells (VSMCs). This phenomenon depends on thrombin serine-protease activity but is independent of PAR-1 and -4 activation and subsequent signaling. The parallel occurrence of cell retraction and cleavage of fibronectin suggests that thrombin-induced apoptosis is consecutive to pericellular proteolysis. These data point to a new potential action of thrombin in the cardiovascular system.
Rossignol
Patrick
P
INSERM U460, CHU X. Bichat, 75877, Paris, Cedex 18, France.
Bouton
Marie-Christine
MC
Jandrot-Perrus
Martine
M
Bryckaert
Marijke
M
Jacob
Marie-Paule
MP
Bezeaud
Annie
A
Guillin
Marie-Claude
MC
Michel
Jean-Baptiste
JB
Meilhac
Olivier
O
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins; D002118:Calcium / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism; D002478:Cells, Cultured; D005109:Extracellular Matrix; D005353:Fibronectins / Q000378:metabolism*; D020287:In Situ Nick-End Labeling; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D011917:Rats, Inbred Lew; D044463:Receptor, PAR-1 / Q000378:metabolism; D013917:Thrombin / Q000494:pharmacology*; D016212:Transforming Growth Factor beta / Q000378:metabolism
D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins; D005353:Fibronectins; D047908:Intracellular Signaling Peptides and Proteins; D010446:Peptide Fragments; D044463:Receptor, PAR-1; D016212:Transforming Growth Factor beta; C101296:prostate apoptosis response-4 protein; D013917:Thrombin; D020778:Matrix Metalloproteinase 2; D002118:Calcium