• Toxicological Research
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• v.8 no.2
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• pp.343-357
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• 1992

Tumor necrosis factor-${\alpha}$(TNF), a polypeptide hormone secreted primarily by activated macrophages, was originally identified on the basis of its ability to cause hemorrhagic necrosis and tumor regression in vivo. Subsequently, TNF has been shown to be an important component of the host responses to infection and cancer and may mediate the wasting syndrome known as cachexia. These systemic actions of TNF are reflected in its diverse effects on target cells in vitro. TNF initiates its diverse cellular actions by binding to specific cell surface receptors. Although TNF receptors have been identified on most of animal cells, regulation of these receptors and the mechanisms which transduce TNF receptor binding into cellular responses are not well understood. Therefore, in the present study, the mechanisms how TNF receptors are being regulated and how TNF receptor binding is being transduced into cellular responses were investigated in rat liver plasma membranes (PM) and ME-180 human cervical carcinoma cell lines. $^{125}I$-TNF bound to high ($K_d=1.51{\pm}0.35nM$)affinity receptors in rat liver PM. Solubilization of PM with 1% Triton X-100 increased both high affinity (from $0.33{\pm}0.04\;to\;1.67{\pm}0.05$ pmoles/mg protein) and low affinity (from $1.92{\pm}0.16\;to\;7.57{\pm}0.50$ pmoles/mg protein) TNF binding without affecting the affinities for TNF, suggesting the presence of a large latent pool of TNF receptors. Affinity labeling of receptors whether from PM or solubilized PM resulted in cross-linking of $^{125}I$-TNF into $M_r$ 130 kDa, 90 kDa and 66kDa complexes. Thus, the properties of the latent TNF receptors were similar to those initially accessible to TNF. To determine if exposure of latent receptors is regulated by TNF, $^{125}I$-TNF binding to control and TNF-pretreated membranes were assayed. Specific binding was increased by pretreatment with TNF (P<0.05), demonstrating that hepatic PM contains latent TNF receptors whose exposure is promoted by TNF. Homologous up-regulation of TNF receptors may, in part, be responsible for sustained hepatic responsiveness during chronic exposure to TNF. As a next step, the post-receptor events induced by TNF were examined. Although the signal transduction pathways for TNF have not been delineated clearly, the actions of many other hormones are mediated by the reversible phosphorylation of specific enzymes or target proteins. The present study demonstrated that TNF induces phosphorylation of 28 kDa protein (p28). Two dimensional soidum dodecyl sulfate-polyacrylamide gel electrophoresis(SDS-PAGE) resolved the 28kDa phosphoprotein into two isoforms having pIs of 6.2 and 6.1. The pIs and relative molecular weight of p28 were consistent with those of a previously characterized mRNA cap binding protein. mRNA cap binding proteins are a class of translation initiation factors that recognize the 7-methylguanosine cap structure found on the 5' end of eukaryotic mRNAs. In vitro, these proteins are defined by their specific elution from affinity columns composed of 7-methylguanosine 5'-triphosphate($m^7$GTP)-Sepharose. Affinity purification of mRNA cap binding proteins from control and TNF treated ME-180 cells proved that TNF rapidly stimulates phosphorylation of an mRNA cap binding protein. Phosphorylation occurred in several cell types that are important in vitro models of TNF action. The mRNA cap binding protein phosphorylated in response to TNF treatment was purifice, sequenced, and identified as the proto-oncogene product eukaryotic initiation factor-4E(eIF-4E). These data show that phosphorylation of a key component of the cellular translational machinery is a common early event in the diverse cellular actions of TNF.

• Journal of Convergence Korean Medicine
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• v.5 no.1
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• pp.55-60
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• 2023

Objectives: This study was performed to investigate the effect of TJGB on the liver of high-fat diet (HFD)-fed mice and the cell viability of HepG2 cells. Methods: After a week adaptation, 8-week-old C57BL/6N mice were fed with a 45% HFD or normal diet for 3 weeks. For the next 9 weeks, the mice were divided into 6 groups: normal diet group; HFD group; HFD plus orlistat group; HFD plus Ephedra sinica Stapf (ES) group; HFD plus low dose of TJGB group; HFD plus high dose of TJGB group. To estimate the effect of TJGB in the liver of HFD-fed mice, the protein expressions of phospho-acetyl-CoA carboxylase (p-ACC) and liver X Receptor (LXR) were determined by Western blot assay. The cell viability of ES and TJG was also evaluated in HepG2 cells. Results: The administration of TJGB had little effect on the protein expressions of p-ACC and LXR in the liver of HFD-fed mice. And the cytotoxicity was showed above 7.8 ㎍/mL in HepG2 cells. Conclusion: Further research is needed to evaluate the mechanism of TJGB on hepatic steatosis and cytotoxicity in HepG2 cells.

• IMMUNE NETWORK
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• v.8 no.1
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• pp.1-6
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• 2008

Apoptosis signal-regulating kinase 1 (ASK1), a mitogen- activated protein kinase kinase kinase, plays pivotal roles in stress responses. In addition, ASK1 has emerged as a key regulator of immune responses elicited by pathogen-associated molecular patterns (PAMPs) and endogenous danger signals. Recent studies have demonstrated that reactive oxygen species (ROS)-dependent activation of ASK1 is required for LPS-stimulated cytokine production as well as extracellular ATP-induced apoptosis in immune cells. The mechanism of ROS-dependent regulation of ASK1 activity by thioredoxin and TRAFs has been well characterized. In this review, we focus on the molecular details of the activation of ASK1 and its involvement in innate immunity.

• Childhood Kidney Diseases
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• v.7 no.1
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• pp.52-59
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• 2003

Purpose : The renin-angiotensin system(RAS) plays an important role in renal growth and development. We have studied the prevalence of renal anomalies and documented the association between karyotype and renal anomalies using IVP and ultrasonography. Furthermore, to investigate the impact of RAS gene polymorphism on renal anomaly in Turner syndrome, we examined the ACE I/D genotype, angiotensinogen(AGT) gene M235T, angiotensin receptor type 1(ATR) gene A1166C. Methods : Cytogenetic analysis was performed in 33 Turner syndrome patients on peripheral blood lymphocytes. Ultrasonography(US) of the kidneys and collecting system and intravenous pyelography(IVP) were perfomed in all patients. Nuclear scintigraphy{Tc 99m dimercaptosuccinic acid(DMSA) scan} was also performed for the definite renal diagnosis if indicated. And, ACE I/D genotype, angiotensinogen(AGT) gene M235T, angiotensin receptor type 1(ATR) gene A1166C were examined by PCR amplification of genomic DNA samples. Results : The prevalence of renal anolmalies in Turner syndrome was 36.4%(12/33). The Karyotype 45, X was observed in 18 of the 33 girls(54.5%), of whom 8(44.4%) had renal anomalies. Mosaic karyotypes were observed in 11(33.3%) and four(12.2%) had a non-mosaic structural aberration of the X chromosome. In this group 4(25.7%) had renal anomalies. More renal anomalies were associated with the 45, X karyotype than those with mosaic/structural abnormalities of X chromosome, but the difference was not statistically significant(P>0.05). And, there was no significant differences in the RAS gene polymorphism and allele frequencies between renal anomaly group and normal group in Turner syndrome. Conclusion : The prevalence of renal anolmalies in Turner syndrome was 36.4%. There is no significant differences in the RAS gene polymorphism and allele frequencies between the renal anomaly group and the normal group in Turner syndrome.

• Asian-Australasian Journal of Animal Sciences
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• v.27 no.12
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• pp.1695-1704
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• 2014

Maternal malnutrition during pregnancy may give rise to female offspring with disrupted ovary functions in adult age. Neonatal ovary development predisposes adult ovary function, yet the effect of maternal nutrition on the neonatal ovary has not been described. Therefore, here we show the impact of maternal protein restriction on the expression of folliculogenic and steroidogenic genes, their regulatory microRNAs and promoter DNA methylation in the ovary of neonatal piglets. Sows were fed either standard-protein (SP, 15% crude protein) or low-protein (LP, 7.5% crude protein) diets throughout gestation. Female piglets born to LP sows showed significantly decreased ovary weight relative to body weight (p<0.05) at birth, which was accompanied with an increased serum estradiol level (p<0.05). The LP piglets demonstrated higher ratio of bcl-2 associated X protein/B cell lymphoma/leukemia-2 mRNA (p<0.01), which was associated with up-regulated mRNA expression of bone morphogenic protein 4 (BMP4) (p<0.05) and proliferating cell nuclear antigen (PCNA) (p<0.05). The steroidogenic gene, cytochrome P450 aromatase (CYP19A1) was significantly down-regulated (p<0.05) in LP piglets. The alterations in ovarian gene expression were associated with a significant down-regulation of follicle-stimulating hormone receptor mRNA expression (p<0.05) in LP piglets. Moreover, three microRNAs, including miR-423-5p targeting both CYP19A1 and PCNA, miR-378 targeting CYP19A1 and miR-210 targeting BMP4, were significantly down-regulated (p<0.05) in the ovary of LP piglets. These results suggest that microRNAs are involved in mediating the effect of maternal protein restriction on ovarian function through regulating the expression of folliculogenic and steroidogenic genes in newborn piglets.

• Asian-Australasian Journal of Animal Sciences
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• v.17 no.5
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• pp.598-602
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• 2004

The Tongcheng pig breed is a famous Chinese indigenous breed. The Ministry of Agriculture of China has filed it as 1 of 19 national key conservation breeds selected from more than 100 Chinese indigenous pig breeds in 2000. In order to improve the reproductive performance, it has been intensively selected to increase the litter size for about 10 years. The population randomly sampled from conservation nucleus of eight families in the Tongcheng pigs was genotyped for identification of their estrogen receptor locus polymorphisms with the PCR-RFLPs method. Only AB heterozygotes and BB homozygotes were detected, and $X^2$ test demonstrated that the locus was in disequilibrium at a significant level (p<0.05). In the present paper, the litter sizes in different parities were regarded as different traits. Holistic status of other unspecific and unidentified genes was estimated by using the statistical methods. Coefficients of kurtosis and skewness showed that the litter size still presented segregating characteristic in the 2nd, 5th, 7th, 8th and 9th parities. Analysis of homogeneity of variance between families confirmed the results for the 5th, 7th and 8th parities. The heritability of litter size for the 1st to 10th parities was estimated with paternal half-sib model and individual estimated breeding values (EBVs) were evaluated by a single trait animal model as well. We found that the averages of EBVs for litter size in each parity did not differ significantly between genotypes, despite the significant difference for original phenotype records in the 3rd, 4th and 5th parities (p<0.05 or p<0.01). The results may be explained by the deduction that the polymorphisms of ESR locus are no longer the important genetic base of litter size variation when the frequency of allele B accumulated in the experience of selection procedure, and further conferring that there exist special genes associated with litter size in the recent Tongcheng pigs population can be made.

• Journal of radiological science and technology
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• v.33 no.4
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• pp.327-334
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• 2010

Exposure during childhood results in higher risk for certain detrimental cancers than exposure during adulthood. We measured entrance skin dose (ESD) under 7-year children undergoing chest imaging and compared the relationship between ESD and age, height, weight, chest thickness. Though it is important to measure chest thickness for setting up the exposure condition of chest examination, it is difficult to measure chest thickness of children. We set up exposure parameters according to age because chest thickness of children has correlation with age. In the exposure parameters, for chest A-P examination under 2 year-children, tube voltage (kVp) in hospital A was higher than that in hospital B while tube current (mAs) was higher in hospital B, thus the ESD values were about 1.7 times higher in hospital B. However, for chest P-A examination over 4 year-children, the tube voltage was 7 kVp higher in hospital B, the tube current were same in all two systems, and focus to image receptor distance (FID) in hospital B (180 cm) was longer than that in hospital A (130 cm), thus the ESD values were 1.4 times higher in hospital A. For same ages, the ESD values for chest A-P examinations were higher than those for chest P-A examinations. Comparing ESD according to age, ESD values were $154{\mu}Gy$, $194{\mu}Gy$ and $138{\mu}Gy$ for children under 1 year, 1 to under 4 years and 4 to under 7 years of age, respectively. These values were lower than reference level ($200{\mu}Gy$) recommended in JART (japan association of radiological technologists), however these were higher than reference values recommended by EC (european commission), NRPB (national radiological protection board) and NIFDS (national institute of food & drug safety evaluation). In conclusion, the values of ESD were affected by exposure parameters from radiographer's past experience more than x-ray system. ESD values for older children were not always higher than those for younger children. Therefore we need to establish our own DRLs (diagnostic reference levels) according to age of the children in order to optimize pediatric patient protection.

• The Korean Journal of Physiology and Pharmacology
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• v.26 no.6
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• pp.447-456
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• 2022

The present study was carried out to investigate the effect of Arctigenin on cell growth and the mechanism of cell death elicited by Arctigenin were examined in FaDu human pharyngeal carcinoma cells. To determine the apoptotic activity of Arctigenin in FaDu human pharyngeal carcinoma cells, cell viability assay, DAPI staining, caspase activation analysis, and immunoblotting were performed. Arctigenin inhibited the growth of cells in a dose-dependent manner and induced nuclear condensation and fragmentation. Arctigenin-treated cells showed caspase-3/7 activation and increased apoptosis versus control cells. FasL, a death ligand associated with extrinsic apoptotic signaling pathways, was up-regulated by Arctigenin treatment. Moreover, caspase-8, a part of the extrinsic apoptotic pathway, was activated by Arctigenin treatments. Expressions of anti-apoptotic factors such as Bcl-2 and Bcl-xL, components of the mitochondria-dependent intrinsic apoptosis pathway, significantly decreased following Arctigenin treatment. The expressions of pro-apoptotic factors such as BAX, BAD and caspase-9, and tumor suppressor -53 increased by Arctigenin treatments. In addition, Arctigenin activated caspase-3 and poly (ADP-ribose) polymerase (PARP) induced cell death. Arctigenin also inhibited the proliferation of FaDu cells by the suppression of p38, NF-κB, and Akt signaling pathways. These results suggest that Arctigenin may inhibit cell proliferation and induce apoptotic cell death in FaDu human pharyngeal carcinoma cells through both the mitochondria-mediated intrinsic pathway and the death receptor-mediated extrinsic pathway.

• Asian-Australasian Journal of Animal Sciences
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• v.29 no.1
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• pp.36-42
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• 2016

Milk-related traits (milk yield, fat and protein) have been crucial to selection of Holstein. It is essential to find the current selection trends of Holstein. Despite this, uncovering the current trends of selection have been ignored in previous studies. We suggest a new formula to detect the current selection trends based on single nucleotide polymorphisms (SNP). This suggestion is based on the best linear unbiased prediction (BLUP) and the Fisher's fundamental theorem of natural selection both of which are trait-dependent. Fisher's theorem links the additive genetic variance to the selection coefficient. For Holstein milk production traits, we estimated the additive genetic variance using SNP effect from BLUP and selection coefficients based on genetic variance to search highly selective SNPs. Through these processes, we identified significantly selective SNPs. The number of genes containing highly selective SNPs with p-value <0.01 (nearly top 1% SNPs) in all traits and p-value <0.001 (nearly top 0.1%) in any traits was 14. They are phosphodiesterase 4B (PDE4B), serine/threonine kinase 40 (STK40), collagen, type XI, alpha 1 (COL11A1), ephrin-A1 (EFNA1), netrin 4 (NTN4), neuron specific gene family member 1 (NSG1), estrogen receptor 1 (ESR1), neurexin 3 (NRXN3), spectrin, beta, non-erythrocytic 1 (SPTBN1), ADP-ribosylation factor interacting protein 1 (ARFIP1), mutL homolog 1 (MLH1), transmembrane channel-like 7 (TMC7), carboxypeptidase X, member 2 (CPXM2) and ADAM metallopeptidase domain 12 (ADAM12). These genes may be important for future artificial selection trends. Also, we found that the SNP effect predicted from BLUP was the key factor to determine the expected current selection coefficient of SNP. Under Hardy-Weinberg equilibrium of SNP markers in current generation, the selection coefficient is equivalent to $2^*SNP$ effect.

• Clinical and Experimental Pediatrics
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• v.52 no.7
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• pp.811-817
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• 2009

Purpose : Inhaled corticosteroids (ICS) are used as first-line agents for the treatment of persistent asthma; however, their use is accompanied by apprehension of potential systemic adverse effects. This study aimed to assess the effects of ICS on bone mineral density (BMD) and bone metabolism in children with asthma. Methods : From February 2008 to September 2008, 26 asthmatic children treated with ICS (ICS group), 15 asthmatic children treated with leukotriene receptor antagonist (LTRA) (LTRA group), and 30 healthy children (Control group) were selected from the Korea University Anam Hospital. BMD and serum bone-specific alkaline phosphatase (BALP) levels were measured. The asthmatic children underwent spirometry and methacholine bronchial challenge test. Results : There were no significant differences in BMD in the lumbar spine (P=0.254) and proximal femur (P=0.297) among the 3 groups. The serum BALP levels were significantly higher in both the ICS (P=0.017) and LTRA (P=0.025) groups than in the Control group. None of the parameters pertaining to ICS use, such as the mean daily dose during the last 6 months, the total cumulative dose, duration of use, and age of commencement of use, showed significant correlations with BMD (P>0.05 for all parameters). Conclusions : We demonstrated that a low dose of ICS does not exert any significant adverse effect on bone metabolism in asthmatic children. These findings support the current recommendations with regard to the use of ICS for asthmatic children.