scholarly journals Kinetics of Receptor-Mediated Endocytosis of Polypeptide Hormones That Governs the Overall Hormone Disposition in the Body : Analysis of the Uptake Process of Epidermal Growth Factor by the Liver and Kidney

1991 ◽  
Vol 111 (12) ◽  
pp. 709-736 ◽  
Author(s):  
Yuichi SUGIYAMA
1993 ◽  
Vol 265 (2) ◽  
pp. E323-E331 ◽  
Author(s):  
H. Kurachi ◽  
H. Adachi ◽  
S. Ohtsuka ◽  
K. Morishige ◽  
K. Amemiya ◽  
...  

Ovariectomy (Ovx) of mice significantly increases the epidermal growth factor (EGF) concentration in the submandibular gland. To elucidate the role of this elevated EGF in obesity of Ovx mice, we examined the effects of sialoadenectomy (Sx) and anti-EGF rabbit antiserum administration on the body weight (BW) gain and carcass fat deposition in Ovx animals. Studies were performed in four groups of mice consisting of control, Ovx, Ovx+Sx, and Ovx+anti-EGF groups. Ovx increased the BW gain compared with the control animals, whereas Sx and anti-EGF significantly reduced it. Although the relative weights (weight ratio to BW) of the liver and kidney were not significantly changed by Ovx, Sx, or anti-EGF treatment of Ovx mice, the relative weights of mesenteric, parametrial, and subcutaneous fat tissues were increased in Ovx mice, and this increase was significantly reduced by Sx or anti-EGF administration. Ovx induced adipocyte hypertrophy, and this effect was eliminated by Sx and anti-EGF. Moreover, acyl-CoA synthetase mRNA level was increased by Ovx, and this increase was reduced by Sx and anti-EGF in mesenteric fat tissue. These findings suggest that elevation of EGF may play a role in the induction of obesity in Ovx mice.


Antioxidants ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 1909
Author(s):  
Min Jeong Kim ◽  
Su Jeong Ha ◽  
Bo Ram So ◽  
Chang-Kil Kim ◽  
Kyung-Min Kim ◽  
...  

The skin acts as the primary defense organ that protects the body from the external environment. Skin cancer is one of the most common cancers in the world. Skin carcinogenesis is usually caused by cell degeneration due to exposure to ultraviolet (UV) radiation, which causes changes in various signaling networks, disrupting the homeostasis of single skin cells. In this review, we summarize the roles of nicotinamide adenine dinucleotide phosphate oxidase (NOX) and epidermal growth factor receptor (EGFR) in UV-induced skin carcinogenesis. Furthermore, we describe the crosstalk that exists between NOX, EGFR, and protein tyrosine phosphatase κ and its oncogenic downstream signaling pathways. Chemoprevention is the use of chemical compounds to recover the healthy status of the skin or delay cancer development. Current evidence from in vitro and in vivo studies on chemopreventive phytochemicals that target NOX, EGFR, or both, as major regulators of skin carcinogenesis will also be discussed.


Cancers ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 1588 ◽  
Author(s):  
Teresa Maria Elisa Modica ◽  
Francesco Dituri ◽  
Serena Mancarella ◽  
Claudio Pisano ◽  
Isabel Fabregat ◽  
...  

Calcium is the most abundant element in the human body. Its role is essential in physiological and biochemical processes such as signal transduction from outside to inside the cell between the cells of an organ, as well as the release of neurotransmitters from neurons, muscle contraction, fertilization, bone building, and blood clotting. As a result, intra- and extracellular calcium levels are tightly regulated by the body. The liver is the most specialized organ of the body, as its functions, carried out by hepatocytes, are strongly governed by calcium ions. In this work, we analyze the role of calcium in human hepatoma (HCC) cell lines harboring a wild type form of the Epidermal Growth Factor Receptor (EGFR), particularly its role in proliferation and in EGFR downmodulation. Our results highlight that calcium is involved in the proliferative capability of HCC cells, as its subtraction is responsible for EGFR degradation by proteasome machinery and, as a consequence, for EGFR intracellular signaling downregulation. However, calcium-regulated EGFR signaling is cell line-dependent. In cells responding weakly to the epidermal growth factor (EGF), calcium seems to have an opposite effect on EGFR internalization/degradation mechanisms. These results suggest that besides EGFR, calcium could be a new therapeutic target in HCC.


Biochemistry ◽  
1983 ◽  
Vol 22 (24) ◽  
pp. 5667-5674 ◽  
Author(s):  
Robert B. Dickson ◽  
John A. Hanover ◽  
Mark C. Willingham ◽  
Ira Pastan

Life Sciences ◽  
1993 ◽  
Vol 52 (13) ◽  
pp. 1135-1139 ◽  
Author(s):  
Koichi Tasaki ◽  
Keisuke Nakata ◽  
Yuji Kato ◽  
Khaleque Newaz Khan ◽  
Satoru Mitsuoka ◽  
...  

1986 ◽  
Vol 102 (1) ◽  
pp. 24-36 ◽  
Author(s):  
W A Dunn ◽  
T P Connolly ◽  
A L Hubbard

Substantial amounts of epidermal growth factor (EGF) are cleared from the circulation by hepatocytes via receptor-mediated endocytosis and subsequently degraded within lysosomes. We have used a combined biochemical and morphological approach to examine the fate of the receptor after exposure to EGF. Polyclonal antibodies were prepared against the purified receptor and their specificity established by immunoprecipitation and immunoblotting techniques. The EGF receptor was then localized by immunofluorescence and immunoperoxidase techniques and quantified on immunoblots. In untreated livers, EGF receptor was restricted to the sinusoidal and lateral surfaces of hepatocytes. 2-4 min after exposure of cells to EGF, the receptor was found in small vesicles (i.e., coated vesicles) as well as larger vesicles and tubules at the cell periphery. By 15 min the receptor was found in multivesicular endosomes located near bile canaliculi. Exposure of hepatocytes to EGF also resulted in a rapid loss of receptor protein from total liver homogenates and a decrease in its half-life from 8.7 h in control livers to 2.5 h. This EGF-induced loss of receptors was not observed when lysosomal proteinases were inhibited by leupeptin or when endosome/lysosome fusion was prevented by low temperature (16 degrees C). In the presence of leupeptin, receptor could be detected in structures identified as lysosomes using acid-phosphatase cytochemistry. All these results suggested rapid internalization of EGF receptors in response to ligand and degradation within lysosomes. However, four times more ligand was degraded at 8 h than the number of high-affinity (Kd of 8-15 nM) EGF-binding sites lost, suggesting either (a) high-affinity receptors were recycled, and/or (b) more than 300,000 receptors were available for EGF uptake. We identified and characterized a latent pool of approximately 300,000 low-affinity receptors (Kd approximately 200 nM) that could be separated on sucrose gradients from the plasma membrane pool of approximately 300,000 high-affinity receptors (Kd of 8-15 nM). Despite the differences in their binding affinities, the high- and low-affinity receptors appeared to be structurally identical and were both EGF-dependent protein kinases. In addition, the dynamics of the low-affinity receptors were consistent with a functional role in EGF uptake and delivery to lysosomes.


1984 ◽  
Vol 100 (1) ◽  
pp. 25-31 ◽  
Author(s):  
B. A. Panaretto ◽  
Z. Leish ◽  
G. P. M. Moore ◽  
D. M. Robertson

ABSTRACT Two groups of three Merino wethers were infused intravenously with either 0·12 mg mouse epidermal growth factor (mEGF)/kg fleece-free body weight or 0·9% (w/v) NaCl over 24 h. Sheep treated with mEGF rejected food during treatment but feed intake was kept equal for both groups. Wool growth and plasma concentrations of mEGF were measured during the experiment. Pieces of skin taken from the wool-growing regions of the body were incubated with radioactive thymidine in order to measure its rate of incorporation into DNA. The skin was then divided at about the level of the sebaceous glands into sections that contained the upper dermis and epidermis (E sections) and those containing the generative wool-follicle bulbs (D sections). No mEGF was detected in the controls whereas mean levels of about 35 μg mEGF/l plasma were detected during the last 4 h of infusion in the protein-treated group. After infusion, wool growth was reduced by about 20% of the mean pretreatment level in the controls and no shedding of wool fibre was evident. In the mEGF-treated sheep, on the other hand, wool growth was depressed by 75–95% of the mean pretreatment level and the fleeces were almost completely cast in all three of the animals, leaving them nude on the wool-growing regions of the body. Wool growth was restored to its pretreatment level in this group about 1 month after infusion. The D sections of skin contributed 50–60% of skin wet weight in controls throughout the experiment. In the mEGF group, however, E sections increased in weight by about 25% and D sections decreased by 25%, relative to pretreatment values, during the 2 weeks after infusion. Both skin sections contributed equally to skin weight thereafter. Whereas the DNA content of E sections tended to increase after mEGF treatment there was a loss of 40%, relative to pretreatment values, in the DNA content of D sections. A significant decrease in thymidine incorporation into DNA in D sections was found, which lasted for at least 72 h after the start of infusion. Thymidine incorporation into E sections was raised during this period and again at about 10–14 days after infusion, when it was increased in both skin sections. We have concluded that the inhibition of wool growth in the mEGF-treated animals was associated with the inhibition of DNA synthesis in the dermal skin sections which contain proliferating cells of wool follicles. J. Endocr. (1984) 100, 25–31


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