Monocrotaline pyrrole protein targets in pulmonary artery endothelial cells.

2009 ◽  
pp. 394-401
Author(s):  
M. W. Lamé ◽  
A. D. Jones ◽  
D. W. Wilson ◽  
S. K. Dunston ◽  
H. J. Segall
Keyword(s):  
Endothelial Cells ◽  
Pulmonary Artery ◽  
Protein Targets ◽  
Monocrotaline Pyrrole

scholarly journals Protein Targets of Monocrotaline Pyrrole in Pulmonary Artery Endothelial Cells

2000 ◽  
Vol 275 (37) ◽  
pp. 29091-29099 ◽  
Author(s):  
Michael W. Lamé ◽  
A. Daniel Jones ◽  
Dennis W. Wilson ◽  
Sheryl K. Dunston ◽  
H. J. Segall
Keyword(s):  
Endothelial Cells ◽  
Pulmonary Artery ◽  
Protein Targets ◽  
Monocrotaline Pyrrole

Monocrotaline pyrrole alters DNA, RNA and protein synthesis in pulmonary artery endothelial cells

1992 ◽  
Vol 262 (6) ◽  
pp. L740-L747 ◽  
Author(s):  
C. M. Hoorn ◽  
R. A. Roth
Keyword(s):  
Endothelial Cells ◽  
Protein Synthesis ◽  
Pulmonary Artery ◽  
Dna Content ◽  
Cell Number ◽  
Synthetic Activity ◽  
Cellular Activity ◽  
Rna And Protein Synthesis ◽  
High Concentrations ◽  
Monocrotaline Pyrrole

Administration of monocrotaline pyrrole (MCTP) to animals results in pulmonary vascular injury. Pulmonary vascular endothelium is a likely target for this pneumotoxicant. Cultured porcine pulmonary artery endothelial cells (PECs) treated with MCTP remain viable but are unable to divide and exhibit an altered morphology. Such responses raise a question about the extent to which affected cells carry out normal functions such as RNA and protein synthesis. Accordingly, the cellular activity of MCTP-treated PECs was examined in this study. PECs were treated with a single administration of MCTP or vehicle, and determinations of cell number, protein, and DNA content were made at times up to 7 days posttreatment. DNA, RNA, and protein synthesis were quantified by incorporation of [3H]thymidine, [3H]uridine, and [3H]leucine, respectively. Increases in cell number that occurred with time in the control cells were reduced in MCTP-treated cells. At 7 days posttreatment, both protein and DNA content increased above control levels. Synthesis of DNA, RNA, and protein continued in all treatment groups throughout the posttreatment period, but cells treated with high concentrations of MCTP showed less synthetic activity than controls during the initial 48 h posttreatment. By 7 days, MCTP-treated cells were producing significantly more DNA, RNA, and protein. These results indicate that cells treated with MCTP continue to synthesize DNA, resulting in an increased DNA content. In addition, treated cells continue to synthesize RNA and translate RNA into protein. Thus, cellular activity is maintained but altered substantially by MCTP exposure.

Characterization of monocrotaline pyrrole-induced DNA cross-linking in pulmonary artery endothelium

1993 ◽  
Vol 264 (5) ◽  
pp. L517-L522 ◽  
Author(s):  
J. G. Wagner ◽  
T. W. Petry ◽  
R. A. Roth
Keyword(s):  
Cell Proliferation ◽  
Endothelial Cells ◽  
Pulmonary Artery ◽  
Pulmonary Vasculature ◽  
Cross Linking ◽  
Toxic Metabolite ◽  
Dependent Manner ◽  
Inhibition Of Proliferation ◽  
Monocrotaline Pyrrole

Monocrotaline pyrrole (MCTP) is a putative, toxic metabolite of the pyrrolizidine alkaloid, monocrotaline (MCT). When given intravenously to rats, it produces a delayed and progressive injury to the vasculature of the lungs that results in pulmonary hypertension and right heart hypertrophy. Dysfunctional endothelium and vascular leak are early signs of overt injury to the lung. When administered to endothelial cell cultures, MCTP causes cell enlargement, delayed and progressive cytotoxicity, and inhibition of proliferation in surviving cells. MCTP is a bifunctional alkylating agent which binds to DNA and other macromolecules. To examine DNA-MCTP interactions in endothelium, MCTP-induced DNA cross-linking was characterized in cultures of porcine endothelial cells (PECs) derived from pulmonary artery. MCTP caused DNA cross-linking in a dose-dependent manner that was consistent with its ability to inhibit cell proliferation. PECs exposed to MCTP for 48 h developed cross-linking that was maximal at 2 days and remained significant through 10 days. Increasing the duration of PEC exposure to the medium to which MCTP had been added was associated with increased DNA cross-linking. These results indicate that MCTP causes DNA cross-linking, which may explain the inhibition of cell proliferation observed in pulmonary endothelial cells in vitro. The long-lasting nature of DNA cross-linking and its dose relatedness are consistent with the delayed and progressive effects of MCTP on endothelial cells in vitro and on pulmonary vasculature in vivo.

Monocrotaline Pyrrole Interacts with Actin and Increases Thrombin-Mediated Permeability in Pulmonary Artery Endothelial Cells

1998 ◽  
Vol 152 (1) ◽  
pp. 138-144 ◽  
Author(s):  
D.W. Wilson ◽  
M.W. Lamé ◽  
S.K. Dunston ◽  
D.W. Taylor ◽  
H.J. Segall
Keyword(s):  
Endothelial Cells ◽  
Pulmonary Artery ◽  
Monocrotaline Pyrrole

Monocrotaline pyrrole targets proteins with and without cysteine residues in the cytosol and membranes of human pulmonary artery endothelial cells

PROTEOMICS ◽  
2005 ◽  
Vol 5 (17) ◽  
pp. 4398-4413 ◽  
Author(s):  
Michael W. Lamé ◽  
A. Daniel Jones ◽  
Dennis W. Wilson ◽  
H. J. Segall
Keyword(s):  
Endothelial Cells ◽  
Pulmonary Artery ◽  
Cysteine Residues ◽  
Human Pulmonary Artery ◽  
Monocrotaline Pyrrole

Monocrotaline Pyrrole Induces Apoptosis in Pulmonary Artery Endothelial Cells

1998 ◽  
Vol 151 (2) ◽  
pp. 236-244 ◽  
Author(s):  
H.C. Thomas ◽  
M.W. Lamé ◽  
S.K. Dunston ◽  
H.J. Segall ◽  
D.W. Wilson
Keyword(s):  
Endothelial Cells ◽  
Pulmonary Artery ◽  
Monocrotaline Pyrrole
Sign in / Sign up

Export Citation Format

Share Document