PDTC, metal chelating compound, induces G1 phase cell cycle arrest in vascular smooth muscle cells through inducing p21Cip1 expression: Involvement of p38 mitogen activated protein kinase

2003 ◽  
Vol 198 (2) ◽  
pp. 310-323 ◽  
Author(s):  
Sung-Kwon Moon ◽  
Sun-Young Jung ◽  
Yung-Hyun Choi ◽  
Young-Choon Lee ◽  
Cam Patterson ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Smooth Muscle ◽  
Protein Kinase ◽  
Vascular Smooth Muscle Cells ◽  
Mitogen Activated Protein Kinase ◽  
Phase Cell ◽  
G1 Phase ◽  
Metal Chelating ◽  
Cycle Arrest ◽  
Mitogen Activated Protein

High Density Lipoproteins Induce Cell Cycle Entry in Vascular Smooth Muscle Cells Via Mitogen Activated Protein Kinase-dependent Pathway

2001 ◽  
Vol 85 (04) ◽  
pp. 730-735 ◽  
Author(s):  
Ralf Junker ◽  
Ewa Pulawski ◽  
Manfred Fobker ◽  
Bodo Levkau ◽  
Arnold von Eckardstein ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Smooth Muscle ◽  
Protein Kinase ◽  
Smooth Muscle Cells ◽  
G Protein ◽  
Vascular Smooth Muscle Cells ◽  
Cell Cycle Progression ◽  
Mitogen Activated Protein Kinase ◽  
Cycle Progression ◽  
Mitogen Activated Protein

SummaryIn this study we found that HDL acts as a potent and specific mitogen in vascular smooth muscle cells (VSMC) by stimulating entry into S-phase and DNA synthesis in a time- and concentration-dependent manner, induction of cyclins D1, E, and A, as well as activation of cyclin D-dependent kinases as inferred from phosphorylation of the retinoblastoma protein (pRb). Moreover, HDL induced activation of the mitogen-activated protein kinase pathway including Raf-, MEK-1, and ERK1/2, as well as the expression of proto-oncogen c-fos, which is controlled by ERK1/2. PD98059, an inhibitor of MEK-1 blocked the mitogenic activity of HDL and cyclin D1 expression. HDL-induced VSMC proliferation, cell cycle progression, cyclin D1 expression, and activation of the Raf-1/MEK-1/ERK1/2 cascade were blocked by pre-incubation of cells with pertussis toxin indicating involvement of trimeric G-protein. By contrast, none of these responses was inhibited by the protein kinase C inhibitor, GF109203X. The mitogenic effects of native HDL were not mimicked by apo A-I, reconstituted HDL containing apo A-I, or cholesterol-containing liposomes. In conclusion, HDL possesses an intrinsic property to induce G-protein- and MAP-kinase-dependent proliferation and cell cycle progression in VSMC. The strong and specific mitogenic effect of HDL should be taken into account, when therapeutic strategies to elevate the plasma level of these lipoproteins are developed.

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