• Bulletin of the Korean Chemical Society
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• 제29권2호
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• pp.342-346
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• 2008

Aurintricarboxylic acid (ATA) prevents apoptosis in a wide range of cell types, including PC12 cells. ATA is known to increase the phosphorylation level of IGF-1 receptor (IGF-1R) and downstream signaling proteins. ATA can translocate across the plasma membrane of PC12 cells and inhibit protein tyrosine phosphatases (PTPs) and, therefore, it is not clear whether ATA exerted its antiapoptotic effect through activation of IGF-1R or by inhibition of cytosolic PTPs. When PC12 cells, deprived of serum, were treated with Fab fragment of anti-IGF-1R antibody to prevent the binding of ATA to the extracellular domain of IGF-1R, ATA was found to penetrate into the cytosolic space of the cells. Under these conditions, the survival-promoting effects of ATA were abolished, and the increase of phosphorylation and characteristic cleavage of IGF-1R were not observed. These results indicate that the antiapoptotic effect of ATA in PC12 cells is due to the binding of ATA to the extracellular domain of IGF-1R and subsequent activation of the IGF-1R, not inhibition of cytosolic PTP(s).

• Fisheries and Aquatic Sciences
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• 제18권4호
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• pp.417-420
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• 2015

We investigated the relationship between viability and IGF-1 receptor (IGF-1R) activity in D-shaped and umbo larvae of the surf clam Spisula sachalinensis after treatment with vitrification solution (VS) or freezing. In a toxicity assay, VS1, containing 5 M dimethyl sulfoxide (DMSO), was very harmful to D-shaped and umbo larvae. However, VS2, containing 5 M ethylene glycol (EG), was not harmful to either larval stage. Although VS2 had a promising toxicity test outcome, none of the larvae survived vitrification. After immersion into VSs and freezing, IGF-1R ${\beta}$-subunits were detected in all larvae; however, tyrosine phosphorylation of intracellular ${\beta}$-subunits was detected only in the control and live groups. These results suggest that activation of IGF-1R may influence surf clam larvae viability.

• Nutrition Research and Practice
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• 제7권4호
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• pp.281-286
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• 2013

We examined the effect of parental folate deficiency on the folate content, global DNA methylation, folate receptor-alpha (FR${\alpha}$), insulin-like-growth factor-2 (IGF-2) and -1 receptor (IGF-1R) in the liver and plasma homocysteine in the postnatal rat. Male and female rats were randomly fed a folic acid-deficient (paternal folate-deficient, PD and maternal folate-deficient, MD), or folic acid-supplemented diet (paternal folate-supplemented, PS and maternal-folate-supplemented, MS) for four weeks. They were mated and grouped accordingly: $PS{\times}MS$, $PS{\times}MD$, $PD{\times}MS$, and $PD{\times}MD$. Pups were killed on day 21 of lactation. The hepatic folate content was markedly reduced in the $PD{\times}MD$ and $PS{\times}MD$ and $PD{\times}MS$ as compared with the $PS{\times}MS$ group. The hepatic global DNA methylation was decreased in the $PD{\times}MS$ and $PS{\times}MD$ groups as much as in the $PD{\times}MD$ group, and all the three groups were significantly lower as compared to the $PS{\times}MS$ group. There were no significant differences in the hepatic FR${\alpha}$, IGF-2 and IGF-1R expressions among the groups. Positive correlations were found between the hepatic folate content and global DNA methylation and protein expressions of FR${\alpha}$, IGF-2 and IGF-1R, whereas an inverse correlation was found between hepatic folate content and plasma homocysteine level in the 3-week-old rat pup. The results of this study show that both paternal and maternal folate deficiency at mating can influence the folate content and global DNA methylation in the postnatal rat liver.

• BMB Reports
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• 제48권6호
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• pp.342-347
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• 2015

The expression of epidermal growth factor receptor (EGFR) is an important diagnostic marker for triple-negative breast cancer (TNBC) cells, which lack three hormonal receptors: estrogen and progesterone receptors as well as epidermal growth factor receptor 2. EGFR transactivation can cause drug resistance in many cancers including TNBC, but the mechanism underlying this phenomenon is poorly defined. Here, we demonstrate that insulin treatment induces EGFR activation by stimulating the interaction of EGFR with insulin-like growth factor receptor 1 (IGF-1R) in the MDA-MB-436 TNBC cell line. These cells express low levels of EGFR, while exhibiting high levels of IGF-1R expression and phosphorylation. Low-EGFRexpressing MDA-MB-436 cells show high sensitivity to insulinstimulated cell growth. Therefore, unexpectedly, insulin stimulation induced EGFR transactivation by regulating its interaction with IGF-1R in low-EGFR-expressing TNBC cells. [BMB Reports 2015; 48(6): 342-347]

• Asian-Australasian Journal of Animal Sciences
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• 제25권7호
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• pp.903-912
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• 2012

In Erhualian and Yorkshire reciprocal cross $F_1$ pig populations, we examined the mRNA expression characteristic of liver-derived IGF-1, IGF-1R, IGF-2, IGF-2R and IGFBP-3 during the embryonic and postnatal developmental periods (E50, E70, E90, D1, D20, D70, D120 and D180). Our results demonstrated that the IGF-system genes mRNA levels exhibited an ontogenetic expression pattern, which was potentially associated with the porcine embryonic development, postnatal growth, organogenesis and even the initiation and acceleration of puberty. The expression pattern of IGF-system genes showed variation in the reciprocal cross ($F_1$ YE and EY pigs). This study also involved the expression features of imprinted genes IGF-2 and IGF-2R. The parent-of-origin effect of imprinted genes was reflected by their differential expression between the reciprocal crosses populations. The correlation analysis also indicated that the regulatory network and mechanisms involved in the IGF system were a complex issue that needs to be more fully explored. A better understanding of IGF system components and their interactive mechanisms will enable researchers to gain insights not only into animal organogenesis but also into somatic growth development and even reproduction.

• The Korean Journal of Physiology and Pharmacology
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• 제20권3호
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• pp.297-304
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• 2016

Klotho functions as a tumor suppressor predominantly expressed in renal tubular cells, the origin of clear cell renal cell carcinoma (ccRCC). Altered expression and/or activity of growth factor receptor have been implicated in ccRCC development. Although Klotho suppresses a tumor progression through growth factor receptor signaling including insulin-like growth factor-1 receptor (IGF-1R), the role of Klotho acting on IGF-1R in ccRCC and its clinical relevance remains obscure. Here, we show that Klotho is favorable prognostic factor for ccRCC and exerts tumor suppressive role for ccRCC through inhibiting IGF-1R signaling. Our data shows the following key findings. First, in tumor tissues, the level of Klotho and IGF-1R expression are low or high, respectively, compared to that of adjacent non-neoplastic parenchyma. Second, the Klotho expression is clearly low in higher grade of ccRCC and is closely associated with clinical outcomes in tumor progression. Third, Klotho suppresses IGF-1-stimulated cell proliferation and migration by inhibiting PI3K/Akt pathway. These results provide compelling evidence supporting that Klotho acting on IGF-1R signaling functions as tumor suppressor in ccRCC and suggest that Klotho is a potential carcinostatis substance for ccRCC.

• 대한방사선방어학회:학술대회논문집
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• 대한방사선방어학회 2011년도 춘계 학술발표회 및 심포지엄
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• pp.18-19
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• 2011

• 한국가축번식학회지
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• 제22권1호
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• pp.81-87
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• 1998

This experiment was carried out with 12 Korean native heifers(8~12month old, body weight, 160~240kg) raised at a farm of Chang-Soo Livestock Cooperatives to evaluate the effects of rGH(recombinant growth hormone) on serum concentrations of growth hormone, estrogen, and IGF-I, weight gain, teat volume gain and processing enzyme activity of IGF-I, binding protein III at 28 day intervals. Animals used were injected with 250mg rGH at 14 day intervals from December to Ferbruary in 1994. The significant difference was found in the group of treatment on the 4th week in the endogenous GH(p<.01) and 8th week in estrogen and IGF-I(p<.05) after injectin of rGH in Korean native heifers. There were significant differences between control group and treatment group in weight and teat volume on 8th week after treatment(p<.05). Processing enzyme activity before injection of rGH were low. However, heifers injected with 250mg of rGH showed that processing enzyme activity of IGF binding protein was highly increased throughout the experiment. Present results suggest that injection of exogenous rGH to heifers can increase the growth performance and udder development of Korean native heifers by the endogenous hormonal changes.

• Asian-Australasian Journal of Animal Sciences
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• 제15권5호
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• pp.725-731
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• 2002

This experiment was performed to understand the changes in plasma leptin in association with plasma IGF-1, body weight and ADG from early growing to late finishing stages of Holstein steers. Blood collection was performed by arterial vein puncture at selected monthly ages of 1 (54 kg), 2.6 (103 kg), 7.2 (205 kg), 13.5 (314 kg), 16.9 (414 kg), 22.2 (550 kg), 24.9 (626 kg) and 27.4 months (695 kg). The blood was analyzed for leptin using the multi-species leptin RIA with recombinant bovine leptin (rbleptin) as standard, plasma IGF-1 was also measured using RIA. Against the standard rbleptin, the multi-species Leptin RIA system's sensitivity, cross reactivity, slope and recovery of 41.0 ng/ml rbleptin in plasma were 4.9 ng/ml, 11.22%, -1.396 and 97.8%, respectively. Plasma leptin measured were more than 5.0 ng/ml, which enable multi-species RIA system to investigate plasma leptin in normal growing steers. Body weight resulted to a highly significant second-degree polynomial relationship with plasma leptin (q=0.54, p<0.0001) and plasma IGF-1 (q=0.44, p<0.0001) from 1 to 27.4 monthly ages. However, the second-degree polynomial curve of plasma leptin and IGF-1 differs showing a concave and convex curvilinear relationship, respectively. ADG was not significantly associated to plasma leptin (r=0.06, p>0.05) and plasma IGF=1 (r=0.06, p>0.05) from 1 to 27.4 monthly ages. Low coefficient, but significant associated increase of plasma leptin and IGF-1 (r=0.12, p<0.008) from 1 to 27.4 months was observed. The uncoordinated increases of plasma IGF-1 at growing and plasma leptin at fattening period, may indicate (1) indirect involvement of endogenous IGF-1 on leptin secretion, and (2) IGF-1 level may signify lean and bone accretion while plasma leptin may mirror body fatness across the monthly ages of Holstein steers.

• Journal of mucopolysaccharidosis and rare diseases
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• 제1권2호
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• pp.54-59
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• 2015

Purpose: Growth hormone (GH) therapy substantially improves several cognitive functions in PWS. However, the molecular mechanisms underlying the beneficial effects of GH on cognition remain unclear in PWS. In this study, we investigated the effects of recombinant human GH on the gene expression of GABAB receptor subunits and GH/insulin-like growth factor (IGF) axis genes in the brain regions of PWS-mimicking mice (Snord116del). Methods: Snord116del mice were injected subcutaneously with 1.0 mg/kg GH or saline, once daily for 7 days. The collected brain tissues were analyzed for mRNA content using quantitative PCR (qPCR) in the cerebellum, hippocampus, and cerebral cortex. Results: GH increased the mRNA expression level of the $GABA_{B1}$ receptor subunit ($GABA_{BR1}$) and IGF-1R in the cerebellum. Furthermore, a significant positive correlation was found between the level of $GABA_{BR1}$ mRNA and the expression of the IGF-1R transcript. GH also induced an increase in the mRNA expression of IGF-2 and IGF-2R in the cerebellum. Conclusion: These data indicate that GH may provide beneficial effects on cognitive function through its influences on the expression of $GABA_{BR1}$ and GH/IGF-1 axis genes in PWS patients.