ABSTRACT
Accumulating evidences have documented that angiogenesis is closely linked to inflammation and regulators of angiogenesis play key roles in various inflammatory conditions. PlGF is an angiogenic protein belonging to the VEGF family and is upregulated mainly in pathologic conditions. Recently, PlGF was discovered having a proinflammatory role in inflammatory arthritis and its serum level drew attention not only as a useful surrogate biomarker but also a potential therapeutic target in atherosclerosis and various cancers. Particularly, PlGF has attractive clinical values because endogenous PlGF is redundant for vascular development and physiological vessel maintenance in healthy adults. However, there have been conflicting results about the efficacy of PlGF inhibition depending on the experimental and clinical settings. Further close investigations for resolving the puzzle of PlGF biology are required.
Subject(s)
Animals , Humans , Arthritis, Rheumatoid/metabolism , Atherosclerosis/metabolism , Biomarkers/metabolism , Inflammation/metabolism , Neoplasms/metabolism , Neovascularization, Pathologic , Pregnancy Proteins/metabolism , Signal TransductionABSTRACT
The placenta is an essential organ that synthesizes several growth and angiogenic factors for its own growth as well as fetal development. It is known that the placenta growth factor (PlGF)is a member of the vascular endothelial growth factor family and is critical for placental growth and fetal development. However, there is little information regarding the expression pattern and cellular localization of PlGF mRNA in rat placenta during pregnancy. The aim of this study was to define the distribution of PlGF mRNA in rat placenta at various gestations. RT-PCR analysis showed that the expression level of PlGF mRNA increased as gestation advanced. Using in situ hybridization histochemistry, positive cells of PlGF mRNA were detected in chorionic villi. PlGF mRNA was expressed in the trophoblast cells and stroma cells surrounding the blood vessels within chorionic villi on day 13 and 15. Also, positive signals of PlGF mRNA were strongly detected in stroma cells of chorionic villi on day 17, 19, and 21. In particular, the density and number of positive signals of PlGF mRNA was significantly increased as gestation advanced. The expression pattern of PlGF mRNA in rat placenta during pregnancy demonstrates that PlGF plays a functional role for placental growth and fetal development during mid-late pregnancy.
Subject(s)
Animals , Female , Pregnancy , Rats , Gene Expression Regulation/physiology , Placenta/metabolism , Pregnancy Proteins/metabolism , RNA, Messenger/metabolism , Rats, Sprague-Dawley , Tissue Distribution/physiologyABSTRACT
C-Terminal carboxyl methylation of a human placental 23 kDa protein catalyzed by membrane-associated methyltransferase has been investigated. The 23 kDa protein substrate methylated was partially purified by DEAE-Sephacel, hydroxyapatite and Sephadex G-100 gel filtration chromatographies. The substrate protein was eluted on Sephadex G-100 gel filtration chromatography as a protein of about 29 kDa. In the absence of Mg2+, the methylation was stimulated by guanine nucleotides (GTP, GDP and GTPgammaS), but in the presence of Mg2+, only GTPgammaS stimulated the methylation which was similar to the effect on the G25K/rhoGDI complex. AFC, an inhibitor of C-terminal carboxyl methylation, inhibited the methylation of human placental 23 kDa protein. These results suggests that the substrate is a small G protein different from the G25K and is methylated on C-terminal isoprenylated cysteine residue. This was also confirmed by vapor phase analysis. The methylated substrate protein was redistributed to membrane after in vitro methylation, suggesting that the methylation of this protein is important for the redistribution of the 23 kDa small G protein for its putative role in intracellular signaling.
Subject(s)
Female , Humans , Pregnancy , Cysteine/metabolism , GTP-Binding Proteins/metabolism , Guanine Nucleotides/pharmacology , Methylation , Placenta/metabolism , Placenta/enzymology , Pregnancy Proteins/metabolism , Protein Methyltransferases/metabolismABSTRACT
La vida media uterina (VMU) de la oxitocina exogena se acepta como una medida indirecta de la vida media plasmatica de la hormona y por tanto, de su depuracion. Hasta el momento no se ha estudiado la VMU en embarazos patologicos. Este trabajo comunica las primeras medidas de la VMU en pacientes con hipertension arterial inducida por el embarazo, clasificada como pre-eclampsia severa. Los valores promedio fueron para el grupo control, 15.1 minutos; y para los casos estudiados, 25.8 minutos. Estos valores permiten calcular una vida media plasmatica aumentada casi al doble en la pre-eclampsia severa. Se discute la fisiopatologia de este hallazgo y se sugiere un posible disturbio metabolico originado en una disminucion de la depuracion renal de la oxitocina