Importance of the liver in plasma clearance of hepatocyte growth factors in rats

1992 ◽  
Vol 263 (5) ◽  
pp. G642-G649 ◽  
Author(s):  
K. X. Liu ◽  
Y. Kato ◽  
M. Narukawa ◽  
D. C. Kim ◽  
M. Hanano ◽  
...  
Keyword(s):  
Binding Sites ◽  
Early Phase ◽  
Trichloroacetic Acid ◽  
Plasma Clearance ◽  
Cell Surfaces ◽  
Receptor Mediated Endocytosis ◽  
Hepatocyte Growth Factors ◽  
Internalization Mechanism ◽  
First Pass ◽  
Hepatocyte Growth

After intravenous administration of 125I-labeled hepatocyte growth factor (HGF), trichloroacetic acid-precipitable radioactivity in the plasma disappeared rapidly with an early phase half-life of 4 min. The amounts of 125I-HGF distributed to the liver, adrenal, spleen, kidney, and lung tissues were much greater than those that could be accounted for by distribution to the extracellular space alone. The first-pass removal of 125I-HGF by the liver was approximately 26%; the liver accounted for approximately 70% of early-phase removal. The hepatic handling was also analyzed using a single-pass perfused liver system. The steady-state extraction ratio of tracer 125I-HGF was 0.48 but dropped to 0.23 in the presence of excess HGF (135 pM), demonstrating hepatic removal saturation of HGF. In the presence of excess HGF, the heparin-washable 125I-HGF, the heparin-resistant and acid-washable 125I-HGF, and the internalized 125I-HGF dropped to 54, 31, and 32% of the control values. The presence of at least two binding sites for HGF on the liver cell surfaces was made clear: the heparin-washable site and the heparin-resistant and acid-washable binding site, considered to have higher affinity for HGF. The internalization of 125I-HGF was observed to some extent even in the presence of excess HGF and phenylarsine oxide, known to be an inhibitor of polypeptides receptor-mediated endocytosis, suggesting the contribution of a relatively nonspecific internalization mechanism as well as receptor-mediated endocytosis.

Demonstration and Quantitation of Pharmacological Inhibition of Pulmonary Uptake of N-lsopropyl-123l-p-lodoamphetamine by Propranolol

1989 ◽  
Vol 28 (03) ◽  
pp. 100-104 ◽  
Author(s):  
S. F. Akber
Keyword(s):  
Binding Sites ◽  
Bolus Injection ◽  
Cell Function ◽  
Lung Pathology ◽  
Lung Uptake ◽  
Pharmacological Inhibition ◽  
Sensitive Index ◽  
Pulmonary Uptake ◽  
First Pass

The first-pass pulmonary extraction values of N-lsopropyl-123l-p-lodoamphetamine (123I-IMP) in pretreated dogs decreases from 90 to 62% as the amount of propranolol increases from 0 to 20 mg. The first-pass pulmonary extraction values of 123I-IMP in dogs with a simultaneous bolus injection of propranolol decreases from 90 to 62% as the amount of propranolol increases from 0 to 10 mg. The pulmonary extraction of 123I-IMP with a simultaneous bolus injection of ketamine and 123I-IMP decreases from 90 to 64% as the ketamine dose increases from 0 to 100 mg. These results suggest that the pulmonary uptake of 123I-IMP may be at least partially mediated by receptors. They also indicate that endothelial metabolic cell function may be a useful index of early lung pathology. Furthermore, studies of the degree of lung uptake may be a sensitive index of pathologic states in which alterations of amine binding sites have occurred.

Gene expression of keratinocyte and hepatocyte growth factors during the healing of rat gastric mucosal lesions

1995 ◽  
Vol 109 (4) ◽  
pp. 1068-1077 ◽  
Author(s):  
Yoshikazu Kinoshita ◽  
Hirohisa Nakata ◽  
Sazzad Hassan ◽  
Masakyo Asahara ◽  
Chiharu Kawanami ◽  
...  
Keyword(s):  
Gene Expression ◽  
Growth Factors ◽  
Gastric Mucosal Lesions ◽  
Hepatocyte Growth Factors ◽  
Mucosal Lesions ◽  
Hepatocyte Growth

scholarly journals AP-2/Eps15 Interaction Is Required for Receptor-mediated Endocytosis

1998 ◽  
Vol 140 (5) ◽  
pp. 1055-1062 ◽  
Author(s):  
Alexandre Benmerah ◽  
Christophe Lamaze ◽  
Bernadette Bègue ◽  
Sandra L. Schmid ◽  
Alice Dautry-Varsat ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Fusion Protein ◽  
Binding Sites ◽  
Fluorescent Protein ◽  
Coated Vesicle ◽  
Mutant Form ◽  
A431 Cells ◽  
Coated Pits ◽  
Receptor Mediated Endocytosis ◽  
Terminal Domain

We have previously shown that the protein Eps15 is constitutively associated with the plasma membrane adaptor complex, AP-2, suggesting its possible role in endocytosis. To explore the role of Eps15 and the function of AP-2/Eps15 association in endocytosis, the Eps15 binding domain for AP-2 was precisely delineated. The entire COOH-terminal domain of Eps15 or a mutant form lacking all the AP-2–binding sites was fused to the green fluorescent protein (GFP), and these constructs were transiently transfected in HeLa cells. Overexpression of the fusion protein containing the entire COOH-terminal domain of Eps15 strongly inhibited endocytosis of transferrin, whereas the fusion protein in which the AP-2–binding sites had been deleted had no effect. These results were confirmed in a cell-free assay that uses perforated A431 cells to follow the first steps of coated vesicle formation at the plasma membrane. Addition of Eps15-derived glutathione-S-transferase fusion proteins containing the AP-2–binding site in this assay inhibited not only constitutive endocytosis of transferrin but also ligand-induced endocytosis of epidermal growth factor. This inhibition could be ascribed to a competition between the fusion protein and endogenous Eps15 for AP-2 binding. Altogether, these results show that interaction of Eps15 with AP-2 is required for efficient receptor-mediated endocytosis and thus provide the first evidence that Eps15 is involved in the function of plasma membrane–coated pits.

Protamine enhances the proliferative activity of hepatocyte growth factor in rats

1998 ◽  
Vol 274 (1) ◽  
pp. G21-G28 ◽  
Author(s):  
Ke-Xin Liu ◽  
Yukio Kato ◽  
Tai-Ichi Kaku ◽  
Kunio Matsumoto ◽  
Toshikazu Nakamura ◽  
...  
Keyword(s):  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Proliferative Activity ◽  
Plasma Clearance ◽  
Mitogenic Response ◽  
Enhancing Effect ◽  
A Cell ◽  
Hepatocyte Growth

The effect of protamine on the proliferative activity of hepatocyte growth factor (HGF) was examined in α-naphthyl isothiocyanate-intoxicated rats. Protamine preinjection increased the hepatocyte labeling index induced by HGF four- to fivefold. A similar effect was also observed in partially hepatectomized rats. Because a cell surface heparin-like substance can bind to HGF and protamine has an affinity for heparin, protamine may affect HGF pharmacokinetics. In fact, protamine injection caused a transient increase in plasma HGF concentrations after administration of HGF and, in vitro, protamine eluted HGF prebound to heparin-Sepharose. Protamine also reduced the plasma clearance of HGF and increased 2.5-fold the exposure of hepatocytes to HGF in vivo. The enhancing effect of protamine on the mitogenic response of hepatocytes to HGF was also observed in vitro (∼2-fold after protamine pretreatment compared with HGF alone), suggesting that the enhancing effect of protamine on HGF-induced liver regeneration results from dual effects exerted by protamine 1) lowering the overall elimination of HGF and 2) directly stimulating hepatocyte mitosis induced by HGF.

Transplantation of Hepatocyte Growth Factor–Modified Dental Pulp Stem Cells Prevents Bone Loss in the Early Phase of Ovariectomy-Induced Osteoporosis

2018 ◽  
Vol 29 (2) ◽  
pp. 271-282 ◽  
Author(s):  
Fanxuan Kong ◽  
Xuefeng Shi ◽  
Fengjun Xiao ◽  
Yuefeng Yang ◽  
Xiaoyan Zhang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Growth Factor ◽  
Bone Loss ◽  
Hepatocyte Growth Factor ◽  
Dental Pulp ◽  
Early Phase ◽  
Dental Pulp Stem Cells ◽  
Hepatocyte Growth

Mechanisms of recovery from mechanical injury of cultured rat hepatocytes

1996 ◽  
Vol 271 (3) ◽  
pp. C721-C727 ◽  
Author(s):  
H. T. Sponsel ◽  
P. S. Guzelian ◽  
S. E. Brown ◽  
R. Breckon ◽  
C. Ray ◽  
...  
Keyword(s):  
Growth Factors ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Primary Cultures ◽  
Rat Hepatocytes ◽  
Integrin Subunit ◽  
Hepatocyte Growth Factors ◽  
Beta 1 Integrin ◽  
Rate Of Recovery ◽  
Hepatocyte Growth

The mechanism(s) whereby hepatocytes restore denuded areas remains unknown. We therefore studied the recovery of denuded areas made in monolayers of primary cultures of rat hepatocytes. Minimal recovery occurred in cells plated on plastic. Plating on Matrigel produced modest recovery (25% at 24 h), whereas plating on a type I collagen substrate resulted in > 70% recovery at 24 h. The rate of recovery on collagen could be attenuated by a monoclonal antibody directed against the extracellular domain of the beta 1-integrin subunit. Monoclonal antibodies directed against CD44 (the hyaluron receptor) and E-cadherin did not influence the rate of recovery. Recovery could be stimulated, in a dose-dependent fashion, by epidermal and hepatocyte growth factors. The effects of epidermal and hepatocyte growth factors to promote recovery occurred in the absence of 5-bromo-2'-deoxyuridine uptake, suggesting a proliferation-independent mechanism. Transforming growth factor-beta 1 inhibited recovery. Exposure to selected cytokines (interleukins 1 and 2), an adenine nucleotide [adenosine 5'-O-(3-thiotriphosphate)], adenosine, pertussis toxin, and selected agents that bind to fibronectin and other matrix component adhesive sites (heparin and the RGD peptide) did not influence the rate of recovery of hepatocytes. However, the peptide DGEA, which can bind to collagen adhesive sites, attenuated recovery. These studies demonstrate that primary cultures of rat hepatocytes require a particular type of extracellular matrix to renew denuded areas and that the beta 1-integrin subunit may be involved in this recovery process. Hepatocyte recovery of denuded areas can be modulated by growth factors in both a stimulatory (epidermal and hepatocyte growth factors) and an inhibitory (transforming growth factor-beta 1) fashion.

scholarly journals Structural Changes in the Deoxyribonucleoprotein (DNP) Complex of Leukocytes from Patients with Infectious Mononucleosis

Blood ◽  
1970 ◽  
Vol 35 (3) ◽  
pp. 322-332 ◽  
Author(s):  
L. BOLUND ◽  
G. GAHRTON ◽  
D. KILLANDER ◽  
R. RIGLER ◽  
BRITTA WAHREN
Keyword(s):  
Acridine Orange ◽  
Acute Phase ◽  
Infectious Mononucleosis ◽  
Binding Sites ◽  
Early Phase ◽  
Structural Changes ◽  
Number Of Binding Sites ◽  
Healthy Persons

Abstract Quantitative microfluorimetric measurements on individual acridine orange (AO) stained cells showed that leukocytes from patients with infectious mononucleosis (IM) exhibited considerably greater AO binding to deoxyribonucleoprotein (DNP) than leukocytes from healthy persons. The higher binding of AO could not be explained by an increase in the amount of DNP in IM cells but by an increased number of binding sites in DNP accessible to AO. This was the result of structural changes in the DNP complex of the IM cells, possibly due to weakened bonds between the DNA and protein moieties of DNP. The binding of AO to IM leukocytes was highest in the early phase of the disease and usually normalized after recovery. However, an increased AO binding of leukocytes from patients after recovery was frequently observed when these cells were exposed to plasma from patients in the acute phase of IM.

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