• Title/Summary/Keyword: Molecular medicine

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Links between accelerated replicative cellular senescence and down-regulation of SPHK1 transcription

  • Kim, Min Kyung;Lee, Wooseong;Yoon, Gang-Ho;Chang, Eun-Ju;Choi, Sun-Cheol;Kim, Seong Who
    • BMB Reports
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    • v.52 no.3
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    • pp.220-225
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    • 2019
  • We have identified a mechanism to diminish the proliferative capacity of cells during cell expansion using human adipose-derived stromal cells (hAD-SCs) as a model of replicative senescence. hAD-SCs of high-passage numbers exhibited a reduced proliferative capacity with accelerated cellular senescence. Levels of key bioactive sphingolipids were significantly increased in these senescent hAD-SCs. Notably, the transcription of sphingosine kinase 1 (SPHK1) was down-regulated in hAD-SCs at high-passage numbers. SPHK1 knockdown as well as inhibition of its enzymatic activity impeded the proliferation of hAD-SCs, with concomitant induction of cellular senescence and accumulation of sphingolipids, as seen in high-passage cells. SPHK1 knockdown-accelerated cellular senescence was attenuated by co-treatment with sphingosine-1-phosphate and an inhibitor of ceramide synthesis, fumonisin $B_1$, but not by treatment with either one alone. Together, these results suggest that transcriptional down-regulation of SPHK1 is a critical inducer of altered sphingolipid profiles and enhances replicative senescence during multiple rounds of cell division.

Mechanism of guanine-specific DNA damage by UVA and its role in photocarcinogenesis and photoaging

  • Kawanishi, Shosuke;Oikawa, Shinji;Hiraku, Yusuke
    • Journal of Photoscience
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    • v.9 no.2
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    • pp.150-153
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    • 2002
  • Solar UV light is a well-known carcinogen. UVA radiation is probably carcinogenic to humans. In addition, recent investigations point to the importance of UVA irradiation in the photoaging. We investigated the mechanism of sequence- specific DNA damage using $\^$32/P-Iabeled DNA fragments in relation to carcinogenesis and aging. Furthermore, we investigated whether UVA accelerates the telomere shortening in human WI-38 fibroblasts. The exposure of double- stranded DNA fragments to 365 nm light in the presence of endogenous sensitizers produced sequence-specific cleavage at the 5' site of 5'-GG-3' and 5'-GGG-3' sequences. In addition, HPLC analysis revealed that sensitizers plus 365 nm light increased the 8-oxodG content of double-stranded DNA. We discuss the mechanisms of guanine-specific DNA damagecaused by excited photosensitizers in relation to carcinogenesis and aging.

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Nuclear Cardiology in Acute Coronary Syndrome (급성관상동맹증후군에서 심장핵의학의 이용)

  • Paeng, Jin-Chul;Lee, Dong-Soo
    • Nuclear Medicine and Molecular Imaging
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    • v.43 no.3
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    • pp.215-221
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    • 2009
  • Nuclear myocardial perfusion imaging is very effective in the evaluation of patients with suspicious acute coronary syndrome (ACS), for adequate diagnosis and treatment. There have been many clinical evidences to support the efficacy and cost-effectiveness. In addition, many authoritative guidelines support the utility of myocardial perfusion imaging in ACS with an appropriate diagnostic protocol. However, with the development of other cardiac imaging modalities, the choice of modality for the diagnosis of suspicious ACS now depends on the availability of each modality in each institute. Newly developed imaging technologies, especially including molecular imaging, are expected to have great potential not only for diagnosis but also for primary, secondary, and tertiary prevention of ACS.

GSTT1 is Deregulated in Left Colon Tumors

  • Coskunpinar, Ender;Canbay, Emel;Oltulu, Yasemin Musteri;Tiryakioglu, Necip Ozan;Bugra, Dursun
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.5
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    • pp.2319-2321
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    • 2014
  • Our aim was to determine GSTT1 expression levels in left colon tumors and paired normal tissue in order to identify specific alterations in GSTT1 mRNA levels. Alterations in GSTT1 expression in twenty-four left-sided colon tumors and paired cancer free tissue were determined by qRT-PCR. Significant fold changes were determined with t-test. When compared with cancer free tissue, left colon cancers showed a significant decrease in GSTT1 expression. However, GSTT1 mRNA levels among different grades increased gradually in correlation with tumor grade. Our results suggest that downregulation of GSTT1 in left-sided colon cancers is an early event and is reversed with cancer progression, probably due to cellular defense mechanisms as a response to changes in the microenvironment.

Novel Glycolipoproteins from Ginseng

  • Pyo, Mi-Kyung;Choi, Sun-Hye;Hwang, Sung-Hee;Shin, Tae-Joon;Lee, Byung-Hwan;Lee, Sang-Mok;Lim, Yoong-Ho;Kim, Dong-Hyun;Nah, Seung-Yeol
    • Journal of Ginseng Research
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    • v.35 no.1
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    • pp.92-103
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    • 2011
  • Ginseng has been used as a general tonic agent to invigorate human body. In the present study, we isolated novel glycolipoproteins from ginseng that activate $Ca^{2+}$-activated $Cl^-$ channel (CaCC) in Xenopus oocytes and transiently increase intracellular free $Ca^{2+}$ concentration ($[Ca^{2+}]_i$) in mouse Ehrlich ascites tumor cells. We named the active ingredients as gintonin. Gintonin exists in at least six different forms. The native molecular weight of gintonin is about 67 kDa but its apparent molecular weight is about 13 kDa, indicating that gintonin might be a pentamer. Gintonin is rich in hydrophobic amino acids. Its main carbohydrates are glucose and glucosamine. Its lipid components are linoleic, palmitic, oleic, and stearic acids. Gintonin actions were blocked by U73122, a phospholipase C inhibitor, 2-aminoethxydiphenyl borate, an inositol 1,4,5-trisphosphate receptor antagonist, or bis (o-aminophenoxy) ethane-N,N,N0,N0-tetracetic acid acetoxymethyl ester, a membrane permeable $Ca^{2+}$ chelator. In the present study, we for the first time isolated novel gintonin and showed the signaling pathways on gintonin-mediated CaCC activations and transient increase of $[Ca^{2+}]_i$. Since $[Ca^{2+}]_i$ as a second messenger plays a pivotal role in the regulation of diverse $Ca^{2+}$-dependent intracellular signal pathways, gintonin-mediated regulations of $[Ca^{2+}]_i$ might contribute to biological actions of ginseng.

General properties and phylogenetic utilities of nuclear ribosomal DNA and mitochondrial DNA commonly used in molecular systematics

  • Hwang, Ui-Wook;Kim, Won
    • Parasites, Hosts and Diseases
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    • v.37 no.4
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    • pp.215-228
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    • 1999
  • To choose one or more appropriate molecular markers or gene regions for resolving a particular systematic question among the organisms at a certain categorical level is still a very difficult process. The primary goal of this review, therefore, is to provide a theoretical information in choosing one or more molecular markers or gene regions by illustrating general properties and phylogenetic utilities of nuclear ribosomal DNA (rDNA) and mitochondrial DNA (mtDNA) that have been most commonly used for phylogenetic researches. The highly conserved molecular markers and/or gene regions are useful for investigating phylogenetic relationships at higher categorical levels (deep branches of evolutionary history). On the other hand, the hypervariable molecular markers and/or gene regions are useful for elucidating phylogenetic relationships at lower categorical levels (recently diverged branches). In summary, different selective forces have led to the evolution of various molecular markers or gene regions with varying degrees of sequence conservation. Thus, appropriate molecular markers or gene regions should be chosen with even greater caution to deduce true phylogenetic relationships over a broad taxonomic spectrum.

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Evidence for the association of peroxidases with the antioxidant effect of p-coumaric acid in endothelial cells exposed to high glucose plus arachidonic acid

  • Lee, Seung-Jin;Mun, Gyeong-In;An, Sang-Mi;Boo, Yong-Chool
    • BMB Reports
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    • v.42 no.9
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    • pp.561-567
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    • 2009
  • Although many plant-derived phenolic compounds display antioxidant effects in biological systems, their mechanism of action remains controversial. In this study, the mechanism by which p-coumaric acid (p-CA) performs its antioxidant action was investigated in bovine aortic endothelial cells under oxidative stress due to high levels of glucose (HG) and arachidonic acid (AA), a free fatty acid. p-CA prevented lipid peroxidation and cell death due to HG+AA without affecting the production of reactive oxygen species. The antioxidant effect of p-CA was not decreased by buthionine-(S,R)-sulfoximine, an inhibitor of cellular GSH synthesis. In contrast, pretreatment with p-CA caused the induction of peroxidases that decomposed t-butyl hydroperoxide in a p-CA-dependent manner. Furthermore, the antioxidant effect of p-CA was significantly mitigated by methimazole, which was shown to inhibit the catalytic activity of 'p-CA peroxidases' in vitro. Therefore, it is suggested that the induction of these previously unidentified 'p-CA peroxidases' is responsible for the antioxidant effect of p-CA.

Characterization of a Cell Line HFH-T2, Producing Viral Particles, from Primary Human Fetal Hepatocytes Infected with Hepatitis B Virus

  • Shim, Jae-Kyoung;Kim, Dong-Wook;Chung, Tae-Ho;Kim, June-Ki;Suh, Jeong-Ill;Park, Chun;Lee, Young-Choon;Chung, Tae-Wha;Song, Eun-Young;Kim, Cheorl-Ho
    • Journal of Microbiology and Biotechnology
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    • v.11 no.2
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    • pp.186-192
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    • 2001
  • A primary culture of human fetal hepatocytes was obtained through a therapeutic abortion process at 26 weeks of gestation period. More than $10^8$ cells were seeded on a plastic plate. These hepatocytes were infected with hepatitis B virus (HBV). The HBV was purified from serum of one chronic HBV carrier. Transformed hepatocytes were subcultured in a 10% FBS-supplemented medium. The morphology of the transformed cell was epithelial-like. The cells from the first pass showed signs of early proliferation and had a latent period of more than 3 months after 6-7 passages. After the rest period, the transformed cell proliferated actively and they were subcultured every three days. Transformed hepatocytes were characterized by detection of the HBV transcript by RT-PCR. The secretion of virions from transformed cells was investigated by PCR with the cell medium. Two types of virions secreted into the culture medium were examined by using the transmission electron microscope. Another approach to study the secretion of virions in to culture medium was carried out with HBV antibody. HBsAg was detected in the culture medium of transformed cells using ELISA and Western blot analyses. These data suggested that the human fetal hepatocyte cell line has been established by infection of HBV, in which this cell line secreted viral particles into the culture medium.

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