• The Korean Journal of Physiology and Pharmacology
• /
• v.15 no.5
• /
• pp.291-297
• /
• 2011

The effect of cyclosporin A (CsA), an immunosuppressant, on human ether-a-go-go-related gene (HERG) channel as it is expressed in human embryonic kidney cells was studied using a whole-cell, patch-clamp technique. CsA inhibited the HERG channel in a concentration-dependent manner, with an $IC_{50}$ value and a Hill coefficient of $3.17{\mu}m$ and 0.89, respectively. Pretreatment with cypermethrine, a calcineurin inhibitor, had no effect on the CsA-induced inhibition of the HERG channel. The CsA-induced inhibition of HERG channels was voltage-dependent, with a steep increase over the voltage range of the channel opening. However, the inhibition exhibited voltage independence over the voltage range of fully activated channels. CsA blocked the HERG channels predominantly in the open and inactivated states rather than in the closed state. Results of the present study suggest that CsA acts directly on the HERG channel as an open-channel blocker, and it acts independently of its effect on calcineurin activity.

• Journal of Marine Bioscience and Biotechnology
• /
• v.6 no.2
• /
• pp.102-109
• /
• 2014

Cetaceans (whales, dolphins, and porpoises) are aquatic mammals that experienced drastic changes during the transition from terrestrial to aquatic environment. Morphological changes include streamlined body, alterations in the face, transformation of the forelimbs into flippers, disappearance of the hindlimbs and the acquisition of flukes on the tail. For a prolonged diving, cetaceans acquired hypoxia-resistance by developing various anatomical and physiological changes. However, molecular mechanisms underlying these adaptations are still limited. CREB-binding protein (CREBBP) is a transcriptional co-activator critical for embryonic development, growth control, metabolic homeostasis and responses to hypoxia. Natural selection analysis of five cetacean CREBBPs compared with those from 15 terrestrial relatives revealed strong purifying selection, supporting the importance of its role in mammals. However, prediction for amino acid changes that elicit functional difference of CREBBP identified three cetacean specific changes localized within a region required for interaction with SRCAP and in proximal regions to KIX domain of CREBBP. Mutations in CREBBP or SRCAP are known to cause craniofacial and skeletal defects in human, and KIX domain of CREBBP serves as a docking site for transcription factors including c-Myb, an essential regulator of haematopoiesis. In these respects, our study provides interesting insights into the functional adaptation of cetacean CREBBP for aquatic lifestyle.

• Toxicological Research
• /
• v.3 no.1
• /
• pp.33-44
• /
• 1987

A fertility study was carried out in Sprague Daxley rats which have been given the intravenous or intraperitoneal injections of rHuIFN-${\alpha}$A, a commecially available therapeutic agent, at dose levels of $1{\times}10^5$, $4{\times}10^5$ and $1.2{\times}10^6$ I.U/kg/day. Male rats were treated with rHuIFN-${\alpha}$A from 60 days before pairing and until the completion of mating. Femal rats received rHuIFN-${\alpha}$A for 22days prior to mating and up to day of gestation. All pregnant females were sacrificed on day 20 of gestation and all fetuses were examined for abnormalities. Both the male and female animals treated with rHuIFN-${\alpha}$A did not show any abnormal responses. No abnormal signs were seen in reproducibility for the rats treated with rHuIFN-${\alpha}$A. No External, internal and skeletal anomalies attributable to rHuIFN-${\alpha}$A were observed in the fetuses. It was concluded that rHuIFN-${\alpha}A$ had no harmful effect on mating, fertilization, implantation, or embryonic development.

• Journal of Science and Technology Studies
• /
• v.5 no.1 s.9
• /
• pp.125-148
• /
• 2005

This paper deals with public understanding of the stem cell cloning discussed in the Internet, based upon the case study of public discourse about Dr. Hwang's international publication of an advanced research of Stem Cell in Korean context. Public understanding of the stem cell cloning in Korea is characterized as follows: (1) it was defined as therapeutic cloning, (2) it was legitimized as a national pride and a potential vehicle for long-term economic performance, (3) ethical issues were criticized by the exclusion of early embryo from human life and the ubiquity of abortion in Korea.

• BMB Reports
• /
• v.51 no.2
• /
• pp.73-78
• /
• 2018

Vascular endothelial growth factor and its receptor (VEGF-VEGFR) system play a critical role in the regulation of angiogenesis and lymphangiogenesis in vertebrates. Each of the VEGF has specific receptors, which it activates by binding to the extracellular domain of the receptors, and, thus, regulates the angiogenic balance in the early embryonic and adult stages. However, de-regulation of the VEGF-VEGFR implicates directly in various diseases, particularly cancer. Moreover, tumor growth needs a dedicated blood supply to provide oxygen and other essential nutrients. Tumor metastasis requires blood vessels to carry tumors to distant sites, where they can implant and begin the growth of secondary tumors. Thus, investigation of signaling systems related to the human disease, such as VEGF-VEGFR, will facilitate the development of treatments for such illnesses.

• Journal of Preventive Medicine and Public Health
• /
• v.47 no.2
• /
• pp.74-83
• /
• 2014

Mercury exists naturally and as a man-made contaminant. The release of processed mercury can lead to a progressive increase in the amount of atmospheric mercury, which enters the atmospheric-soil-water distribution cycles where it can remain in circulation for years. Mercury poisoning is the result of exposure to mercury or mercury compounds resulting in various toxic effects depend on its chemical form and route of exposure. The major route of human exposure to methylmercury (MeHg) is largely through eating contaminated fish, seafood, and wildlife which have been exposed to mercury through ingestion of contaminated lower organisms. MeHg toxicity is associated with nervous system damage in adults and impaired neurological development in infants and children. Ingested mercury may undergo bioaccumulation leading to progressive increases in body burdens. This review addresses the systemic pathophysiology of individual organ systems associated with mercury poisoning. Mercury has profound cellular, cardiovascular, hematological, pulmonary, renal, immunological, neurological, endocrine, reproductive, and embryonic toxicological effects.

• Genomics & Informatics
• /
• v.5 no.1
• /
• pp.1-5
• /
• 2007

Embryonic stem cells can be differentiated into various types of cells, requiring a tight regulation of transcription. Biomarkers related to each lineage of cells are used to guide the differentiation into neural or any other fates. In previous experiments, we reported the guided differentiation (GD)-specific genes by comparing profiles of random differentiation (RD). Interestingly 68% of differentially expressed genes in GD overlap with that of RD, which makes it difficult for us to separate the lineages by examining several markers. In this paper, we design a prediction model to identify the differentiation into neural fates from any other lineage. From the profiles of 11,376 genes, 203 differentially expressed genes between neural and random differentiation were selected by random variance T-test with 95% confidence and 5% false discovery rate. Based on support vector machine algorithm, we could select 79 marker genes from the 203 informative genes to construct the optimal prediction model. Here we propose a prediction model for the prediction of neural fates from random differentiation which is constructed with a perfect accuracy.

• Archives of Pharmacal Research
• /
• v.22 no.5
• /
• pp.454-458
• /
• 1999

TR8 is a recently identified member of the tumor necrosis factor (TNF) receptor superfamily. TR8 seems to play important roles in bone metabolism as stimulation of this receptor with its ligand, TL8 or osteoclast differentiation factor (ODF), induced the differentiation and activation of osteoclasts. Despite its important biological functions, the biochemcial events ensuing form TR8 activation have not been revealed in detail. Most of TNF receptor family proteins provoke the activation of the NF-$textsc{k}$B transcription factor. In the present study, we examined the signaling potential of TR8 to induce NF-B activation. When overexpressed in a human embryonic kidney cell line by transient transfection, TR8 caused a strong activation of NF-$textsc{k}$B, which was further increased upon stimulation with TL8. The TR8-induced NF-B activation was abrogated by the co-expression of the TRAF6 mutnat lacking the Ring and zinc finger domains and that of the kinase-inactive mutant NIK. Taken together, our study suggests that the presence of intact TRAF6 and the kiase activity of NIK may be essential for TR8 to induce NF-$textsc{k}$B activation.

• Journal of Ginseng Research
• /
• v.37 no.2
• /
• pp.201-209
• /
• 2013

Ginsenoside, one of the active ingredients of Panax ginseng, has a variety of physiologic and pharmacologic effects. The purpose of this study was to explore the effects of ginsenoside Rd (G-Rd) on melastatin type transient receptor potential 7 (TRPM7) channels with respect to the proliferation and survival of AGS and MCF-7 cells (a gastric and a breast cancer cell line, respectively). AGS and MCF-7 cells were treated with different concentrations of G-Rd, and caspase-3 activities, mitochondrial depolarizations, and sub-G1 fractions were analyzed to determine if cell death occurred by apoptosis. In addition, human embryonic kidney (HEK) 293 cells overexpressing TRPM7 channels were used to confirm the role of TRPM7 channels. G-Rd inhibited the proliferation and survival of AGS and MCF-7 cells and enhanced caspase-3 activity, mitochondrial depolarization, and sub-G1 populations. In addition, G-Rd inhibited TRPM7-like currents in AGS and MCF-7 cells and in TRPM7 channel overexpressing HEK 293 cells, as determined by whole cell voltage-clamp recordings. Furthermore, TRPM7 overexpression in HEK 293 cells promoted G-Rd induced cell death. These findings suggest that G-Rd inhibits the proliferation and survival of gastric and breast cancer cells by inhibiting TRPM7 channel activity.

• Bulletin of the Korean Chemical Society
• /
• v.31 no.10
• /
• pp.2771-2775
• /
• 2010

We present a rapid biogenic method for the production of nanoscale gold particles using pear extract. The formation and stability of pear-derived gold nanoparticles (Pear-AuNPs) were monitored by ultraviolet-visible spectroscopy. Their morphology, elemental composition and crystalline phase were determined by transmission electron microscopy, energy-dispersive X-ray spectroscopy and selected area electron diffraction. The average core size of crystalline Pear-AuNPs was in the range of $10{\pm}5\;nm$ and the observed morphology was spherical. The X-ray photoelectron spectrum showed a strong peak for the pure 'Au' phase. The circular dichroism spectrum indicated the natural capping ability of the pear extract, which generated peptide-gold nanoparticles. These nanoparticles were stable in aqueous solution for two months. A cell viability assay of Pear-AuNPs showed biocompatibility with human embryonic kidney 293 cells. Accordingly, this eco-friendly process for the bio-mimetic production of Pear-AuNPs is nontoxic in nature; consequently, it will find potential application in nano-biotechnology.