Transforming growth factor beta 1 induces apoptotic cell death in cultured human umbilical vein endothelial cells with down-regulated expression of bcl-2.
Transforming growth factor beta 1 (TGF-beta 1) is a potent growth inhibitor of human umbilical vein endothelial cells (HUVEC). We investigated whether apoptosis is involved in the TGF-beta 1 mediated HUVEC growth inhibition. Using immunofluorescence microscopy and staining by propidium iodide, we showed HUVEC treated with TGF-beta 1 contained characteristic apoptotic nuclei with condensation of chromatin. FACS analysis demonstrated that the number of cells with hypodiploid DNA contents were increased in HUVEC treated with TGF-beta 1. The DNA fragmentation assay exhibited typical ladder formation in TGF-beta 1-treated HUVEC. Using Western blot analysis, the expression of bcl-2 on HUVEC was down-regulated by TGF-beta 1-treatment. These findings suggest that TGF-beta 1 regulates the growth of HUVEC by inducing apoptosis accompanied with down-regulation of bcl-2 expression.
Tsukada
T
T
First Department of Internal Medicine, Nagasaki University School of Medicine, Japan.
Eguchi
K
K
Migita
K
K
Kawabe
Y
Y
Kawakami
A
A
Matsuoka
N
N
Takashima
H
H
Mizokami
A
A
Nagataki
S
S
D017209:Apoptosis / Q000187:drug effects*; D002467:Cell Nucleus / Q000187:drug effects / Q000648:ultrastructure; D002478:Cells, Cultured; D004247:DNA / Q000187:drug effects / Q000378:metabolism; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000187:drug effects*; D008856:Microscopy, Fluorescence; D011505:Protein-Tyrosine Kinases / Q000096:biosynthesis; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis*; D019253:Proto-Oncogene Proteins c-bcl-2; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014471:Umbilical Veins
D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016212:Transforming Growth Factor beta; D004247:DNA; D011505:Protein-Tyrosine Kinases