• Title/Summary/Keyword: Mechanism reduction

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AMP-activated Kinase Regulates Adipocyte Differentiation Process in 3T3-L1 Adipocytes Treated with Selenium (AMP-activated protein kinase가 셀레늄으로 처리된 3T3-L1 지방세포의 분화과정 억제에 관한 연구)

  • Park, Song-Yi;Hwang, Jin-Taek;Lee, Yun-Kyoung;Kim, Young-Min;Park, Ock-Jin
    • Journal of Life Science
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    • v.19 no.4
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    • pp.423-428
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    • 2009
  • Selenium was investigated using human origin preadipocytes to see whether it possesses preventive or therapeutic effects for obesity. Unveiling the potential of selenium in the reduction of adipogenesis can help predict the therapeutic capabilities of selenium in obesity. In the present study, the molecular mechanism of the inhibition of adipogenesis by selenium was explored to unravel the involvement of the AMP-activated protein kinase. There is emerging evidence that AMPK, a sensor of cellular energy status, is a possible molecular target of controlling adipocyte differentiation on the basis of discovery that AMPK is responsible for the major metabolic responses to exercise, and integration of nutritional and hormonal signals to modulate feeding behavior or energy expenditure in the hypothalamus. Treatment of selenium resulted in inhibition of the adipocyte differentiation process and induction of mature apoptosis in 3T3-L1 adipocytes. We hypothesized that selenium may exert anti-adipogenic potential though modulating AMPK. We have found that selenium significantly activated AMPK and phosphorylated its substrate acetyl-CoA carboxylase ($ACC-serine^{79}$) during the inhibitory process of adipocytes. Also, the inhibition process of adipocyte differentiation by selenium was comparable to either reveratrol or a synthetic AMPK activator, AICAR (5-aminoimidazole-4-carboxamide-1-${\beta}$-D-ribofuranoside). To evaluate the involvement of AMPK in anti-lipogensis, we applied AICAR and Compound C, an AMPK inhibitor, to 3T3-L1-adipocytes and found that AMPK is required for the adipocyte differentiation blocking process. These results suggest that selenium has a potential to control adipogenesis and that this effect is mediated by AMPK, an essential kinase for both inhibition of adipocyte differentiation and apoptosis of mature adipocytes.

A Co-inhibitory Molecule, B7-H4, Synergistically Potentiates Oral Tolerance by Inducing CD4+CD25+FoxP3+ T Cells

  • Wen, Lanying;Yang, Sung-Yeun;Choi, Jae-Kyoung;Kim, Young-Hee;Kwon, Eun-Hee;Lee, Hyun-Ji;Jeoung, Hae-Young;Hwang, Du-Hyeon;Hwang, Dong-Jin;Choi, In-Hak
    • IMMUNE NETWORK
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    • v.8 no.1
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    • pp.21-28
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    • 2008
  • Background: A co-inhibitory molecule, B7-H4, is believed to negatively regulate T cell immunity by suppressing T cell proliferation and inhibiting cytokine production. However, the mechanism behind B7-H4-mediated tolerance remains unclear. Methods: Balb/c $(H-2^d)$ mice were fed with dendritic cell line, DC2.4 $(H-2^d)$ every day for 10 days. Meantime, mice were hydrodynamically injected with recombinant plasmid expressing B7-H4 fusion protein (B7-H4.hFc) or hFc via tail vein. One day after last feeding, mice were immunized with allogeneic B6 spleen cells. 14 days following immunization, mice were challenged with B6 spleen cells to ear back and the ear swelling was determined the next day. Subsequently, a mixed lymphocyte reaction (MLR) was also performed and cytokines profiles from the reaction were examined by sandwich ELISA. Frequency of immunosuppressive cell population was assayed with flow cytometry and mRNA for FoxP3 was determined by RT-PCR. Results: Tolerant mice given plasmid expressing B7-H4.hFc showed a significant reduction in ear swelling compared to control mice. In addition, T cells from mice given B7-H4.hFc plasmid revealed a significant hyporesponsiveness of T cells against allogeneic spleen cells and showed a significant decrease in Th1 and Th2 cytokines such as IFN-${\gamma}$, IL-5, and TNF-${\alpha}$. Interestingly, flow cytometric analysis showed that the frequency of CD4+CD25+FoxP3+ Tregs in spleen was increased in tolerant mice given recombinant B7-H4.hFc plasmid compared to control group. Conclusion: Our results demonstrate that B7-H4 synergistically potentiates oral tolerance induced by allogeneic cells by increasing the frequency of FoxP3+ CD4+CD25+ Treg and reducing Th1 and Th2 cytokine production.

Effect of ω3-Fatty Acid Desaturase Gene Expression on Invasion and Tumorigenicity in Human Tongue Squamous Cell Carcinoma Cells (인체 혀의 편평세포암 세포에서 ω3-fatty acid desaturase 유전자 발현이 침윤 및 종양형성에 미치는 영향)

  • Hong, Tae-Hwa;Shin, Soyeon;Han, Seung-Hyeon;Hwang, Byung-Doo;Lim, Kyu
    • Journal of Life Science
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    • v.28 no.8
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    • pp.945-954
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    • 2018
  • Omega-3 polyunsaturated fatty acids (${\omega}3$-fatty acid) have been found to possess anticancer properties in a variety of cancer cell lines and animal models, but their effects in human tongue squamous cell carcinomas (SCCs) remain unclear. This study was designed to examine the effect of ${\omega}3$-fatty acid desaturase (fat-1) gene expression on invasion and tumorigenicity in human tongue SCC cells and the molecular mechanism of its action. Docosahexaenoic acid (DHA) treatment inhibited in vitro invasion in a dose-dependent manner. In zymography, matrix metalloproteinase-9 (MMP-9) and Matrix metallopeptidase-2 (MMP-2) activities were reduced, and MMP-9 and MMP-2 promoter activities were inhibited by the DHA treatment. In addition, cyclooxygenase-2 (COX-2) and vascular endothelial growth factor (VEGF) promoter reporter activities were inhibited in SCC-4 and SCC-9 cells after the DHA treatment. To investigate the effect of a high level of endogenous ${\omega}3$ fatty acids, a stable SCC-9 cell line expressing the ${\omega}3$-desaturase gene (fSCC-9sc) was generated. The growth rate and colony-forming capacity of fSCC-9sc were remarkably decreased as compared with those of fSCC-9cc. Likewise, the tumor size and volume of fSCC-9sc implanted into nude mice were significantly inhibited, with increases in the cell death index. Furthermore, a transwell chamber invasion assay showed a reduction in cell invasion of the fSCC-9sc lines when compared with that of the fSCC-9cc line. These findings suggested that fat-1 gene expression inhibited tumorigenicity, as well as invasion in human tongue SCC cells. Thus, utilization of ${\omega}3$ fatty acids may represent a promising therapeutic approach for chemoprevention and the treatment of human tongue SCCs.

Involvement of Serotonergic Mechanism in the Nucleus Tractus Solitarius for the Regulation of Blood Pressure and Heart Rate of Rats (흰쥐의 혈압 및 심박동수 조절에 대하여 Nucleus Tractus Solitarius 부위의 Serotonin성 기전의 역할)

  • Lee, Yong-Kyu;Hong, Ki-Whan;Yoon, Jae-Soon
    • The Korean Journal of Pharmacology
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    • v.25 no.1
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    • pp.1-11
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    • 1989
  • In this study, it was aimed to investigate the role of serotonergic neurotransmission in nucleus tractus solitarius (NTS) for the central regulation of blood pressure and heart rate and its involvement in baroreceptor reflex activation in rats. A microinjection of 5-hydroxytryptamine (5-HT) into the NTS produced decreases in blood pressure and heart rate. Maximal decreases were $34.4{\pm}1.6$ mmHg and $41.7{\pm}10.2$ beats per min by 300 pmol of 5-HT. Microinjections of ${\alpha}-methylnor-adrenaline$ $({\alpha}-MNE)$ and clonidine manifested similar decreases in blood pressure and heart rate. The hypotensive and bradycardial effects of 5-HT were blocked by previous applications of 5-HT antagonists, ritanserin, methysergide and ketanserin into the NTS, respectively. By pretreatment with reserpine and 6-hydroxydopamine (6-OHDA, i.c.v.), both hypotensive and bradycardial effects of 5-HT were significantly attenuated. Pretreatment with 5, 7-dihydroxytryptamine (5,7-DHT, i.c.v.) enhanced the hypotensive and bradycardial effects of 5-HT. Similarly, following pretreatment with 6-OHDA, the effects of clonidine were increased. Pretreatment either with 5,7-DHT or 6-OHDA significantly attenuated the sensitivity of baroreflex produced either by phenylephrine or by sodium nitroprusside. When either 5,7-DHT or 6-OHDA was injected into the NTS $(5,7-DHT;\;8{\mu}g\;6-OHDA;\;10{\mu}g)$, both of the baroreflex sensitivities were impaired. In the immunohistochemical study, the injection of 6-OHDA into the the NTS led to reduction of axon terminal varicosity, however, the injection did not reduce the numbers of catecholaminergic cell bodies. Likewise, when 5,7-DHT was injected into the NTS, the varicosity of serotonergic axon terminals was markedly reduced. Based on these results, it is suggested that (1) stimulation of serotonergic receptors in the NTS leads to decreases in blood pressure and heart rate as observed with the stimulation of catecholaminergic system, (2) both serotonergic and catecholaminergic receptors may be located postsynaptically, and (3) the serotonergic neurons as well as catecholaminergic neurons may have a close relevance for the activation of baroreflex.

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EFFECT OF 10% CARBAMIDE PEROXIDE ON DENTIN (상아질에 대한 10% Carbamide peroxide가 미치는 영향)

  • Seo, Sang-Woo;Kown, Yong-Hoon;Kim, Hyun-Jung;Nam, Soon-Hyeun;Kim, Kyo-Han;Kim, Young-Jin
    • Journal of the korean academy of Pediatric Dentistry
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    • v.30 no.3
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    • pp.423-430
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    • 2003
  • The teeth bleaching with bleaching agent is widely used at recent times. Until yet the exact mechanism of the bleaching agent isn't known but it is thought that is by the complex reduction-oxidation reaction of the decomposed free radical from bleaching agent through various ways. In other words, it is supposed that the teeth are whitened by agent's changing chemical structures of stain-causing materials. The purpose of this study is to exam the change of the dentinal character by bleaching agent and to evaluate the safety of this agent. For this study, after applying 10% carbamide peroxide to enamel of human premolar for 6 hours a day for 2 weeks we examined changes of surface morphology, microhardness, composition and contents of minirals in human dentin using SEM, microhardness tester, FT-Raman spectrometer and EPMA and got following results. There was no significant difference in surface morphologic change when we examined the effect of 10% carbamide peroxide which penetrated into dentin after applied on enamel surface comparing with result from specimen in distilled water No change was shown on the surface of peritubular and intertubular dentin within the nanometeric range. The microhardness between bleached teeth and teeth stored in distilled water showed no statistically significant difference FT-Raman spectra of dentin exhibited no change of the component in human dentin. Only the least change in peaks of organic and inorganic materials were detected in Raman intencity. The total content of mineral elements in dentin with no treatment, stored only in distilled water and stored in distilled water after bleaching were $98.73{\pm}1.89,\;98.56{\pm}2.11\;and\;97.47{\pm}2.51$ respectively. Also they showed no statistically significant difference. From above results, the effect of 10% carbamide peroxide bleaching on structure of dentin is very low and the results may confirm the safety of this bleaching agent.

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The effect of heat shock protein 70 on inducible nitric oxide synthase during sepsis in rats (백서 패혈증 모델에서 HSP70의 과도 발현이 iNOS의 발현에 미치는 효과에 관한 연구)

  • Lee, Yong-Keun;Ahn, Yung;Leem, Dae-Ho;Baek, Jin-A;Ko, Seung-O;Shin, Hyo-Keun
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • v.36 no.5
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    • pp.346-352
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    • 2010
  • Introduction: Heat shock protein70 (HSP70) is a highly conserved family of proteins produced after a variety of stresses. Many studies reported that the overexpression of HSP70 can improve the prognosis of the patients with sepsis through a reduction of the nitric oxide concentration. However, these results only revealed the effect of HSP70 and nitric oxide. No studies have examined the relationship between HSP70 and nitric oxide. The aim of this study was to evaluate the effect of the overexpression of HSP70 on the expression of inducible nitric oxide synthase and the nitric oxide concentration. In addition, the mechanism of the relationship of HSP70 and inducible nitric oxide synthase (iNOS) in sepsis was examined. Materials and Methods: The experiments were performed on male sprague-dawley rats. Sepsis was induced by a cecal ligation and puncture (CLP). Glutamine (GLN) or saline was administered 1 hour after the initiation of sepsis. Serum and lung tissues were acquired from the rats 12 hours or 24 hours after the initiation of sepsis. The nitric oxide concentration, the expression of HSP70 in lung, and the gene expression of iNOS in lung were analyzed. The three groups, sham operation, CLP and CLP+GLN, were compared. Results: Compared to the other groups, in CLP+GLN, GLN administered after the initiation of sepsis enhanced the expression of HSP70 in the lung at 12 hours ($47.19{\pm}10.04$ vs. $33.22{\pm}8.28$, P=0.025) and 24 hours ($47.06{\pm}10.60$ vs. $31.90{\pm}4.83$, P=0.004). In CLP+GLN, GLN attenuated the expression of iNOS messenger RNA (mRNA) in the lung at 12 hours ($5,513.73{\pm}1,051.60$ vs. $4,167.17{\pm}951.59$, P=0.025) and 24 hours ($18,740.27{\pm}8,241.20$ vs. $9,437.65{\pm}2,521.07$, P=0.016), and reduced the concentration of nitric oxide in the serum at 12 hours ($0.86{\pm}0.48$ vs. $3.82{\pm}2.53$, P=0.016) and 24 hours ($0.39{\pm}0.25$ vs. $1.85{\pm}1.70$, P=0.025). Conclusion: The overexpression of HSP70 induced by the administration of GLN in sepsis attenuates the expression of the iNOS gene but reduces the nitric oxide concentration.

Lipolytic Effect of Methanol Extracts from Luffa cylindrica in Mature 3T3-L1 Adipocytes (분화된 3T3-L1 세포에서 수세미오이 메탄올 추출물의 지방분해 효과)

  • Cha, Seung-Youn;Jang, Ja-Young;Lee, Yoo-Hyun;Lee, Gyu-Ok;Lee, Ho-Joon;Hwang, Kwon-Tack;Kim, Yong-Jae;Jun, Woo-Jin;Lee, Jeong-Min
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.39 no.6
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    • pp.813-819
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    • 2010
  • The intracellular lipid droplets were stained with Oil Red O dye and quantified. Compared to the control, lipid accumulation was significantly decreased by 19.4% with the treatment of LCM at the concentration of $1000\;{\mu}g$/mL. Intracellular triglyceride (TG) level was also reduced by 21% at the concentration of $1000\;{\mu}g$/mL. To determine the mechanism for the reduction in TG content, levels of glucose uptake and glycerol release were measured. Incubation of the 3T3-L1 adipocytes with LCM did not affect the cellular uptake of glucose. However, the level of free glycerol released into the cultured medium drastically increased by 24.3% with the treatment of LCM. In subsequent measurements using quantitative real-time PCR, mRNA levels of hormone-sensitive lipase (HSL) and adipose triglyceride lipase (ATGL) except lipoprotein lipase (LPL) were significantly elevated at higher concentration. These results suggest that LCM partially stimulates the lipolysis through the induction of HSL and/or ATGL gene expression, resulting in the reduced lipid accumulation and increased glycerol release.

The Historical Study of Headache in Chinese Ming Dynasty (명대의가(明代醫家)들의 두통(頭痛)에 대한 인식변화에 관한 연구)

  • Chun, Duk-Bong;Maeng, Woong-Jae;Kim, Nam-Il
    • The Journal of Korean Medical History
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    • v.24 no.1
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    • pp.43-56
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    • 2011
  • Everyone once in a life experience headaches as symptoms are very common. According to a study in a country of more than a week and as many as those who have experienced a headache amounts to 69.4%. In addition, the high reported prevalence of migraine in 30s for 80% of all migraine sufferers daily life interfere with work or was affected. In Western medicine, the cause of headaches is traction or deformation of pain induced tissue like scalp, subcutaneous tissue, muscle, fascia, extracranial arteriovenous, nerves, periosteum. But it turns out there are not cause why pain induced tissue is being tracted or deformated. Therefore, most of the western-therapy is mainly conducted with regimen for a temporary symptom reduction. Therefore, I examined how it has been developed in Chinese Ming Dynasty, the perception of headache, change in disease stage and an etiological cause. Oriental medicine in the treatment of headache is a more fundamental way to have an excellent treatment. The recognition of head in "素問($s{\grave{u}}$ $w{\grave{e}}n$)" and "靈樞($l{\acute{i}}ng$ $sh{\bar{u}}$)" began to appear in 'Soul-神($sh{\acute{e}}n$) dwelling place' and 'where to gather all the Yang-'諸陽之會($zh{\bar{u}}$ $y{\acute{a}}ng$ $zh{\bar{i}}$ $hu{\grave{i}}$)'. Also, head was recognized as '六腑($li{\grave{u}}f{\check{u}}$) 淸陽之氣($q{\bar{i}}ng$ $y{\acute{a}}ng$ $zh{\bar{i}}$ $q{\grave{i}}$) and 五臟($w{\check{u}}$ $z{\grave{a}}ng$) 精血($j{\bar{i}}ng$ $xu{\grave{e}}$) gathering place'. More specific structures such as the brain is considered a sea of marrow(髓海-$su{\check{i}}$ $h{\check{a}}i$) in "內經($n{\grave{e}}i$ $j{\bar{i}}ng$)" and came to recognized place where a stroke occurs. Accompanying development of the recognition about head, there had been changed about the perception of headache and the recognition of the cause and mechanism of headache. And the recognition of headache began to be completed in Ming Dynasty through Jin, Yuan Dynasty. Chinese Ming Dynasty, specially 樓英($l{\acute{o}}u$ $y{\bar{i}}ng$), in "醫學綱目($y{\bar{i}}xu{\acute{e}}$ $g{\bar{a}}ngm{\grave{u}}$)", first enumerated prescription in detail by separating postpartum headache. and proposed treatment of headache especially due to postpartum sepsis(敗血-$b{\grave{a}}i$ $xu{\grave{e}}$). 許浚($x{\check{u}}$ $j{\grave{u}}n$) accepted a variety of views without impartial opinion in explaining one kind of headache in "東醫寶鑑($d{\bar{o}}ng-y{\bar{i}}$ $b{\check{a}}oji{\grave{a}}n)$" 張景岳($zh{\bar{a}}ng$ $j{\check{i}}ng$ $yu{\grave{e}}$), in "景岳全書($j{\check{i}}ng$ $yu{\grave{e}}$ $qu{\acute{a}}nsh{\bar{u}}$)", established his own unique classification system-新舊表裏($x{\bar{i}}nji{\grave{u}}$ $bi{\check{a}}ol{\check{i}}$)-, and offered a clear way even in treatment. Acupuncture treatment of headache in the choice of meridian has been developed as a single acupuncture point. Using the classification of headache to come for future generation as a way of locating acupoints were developed. Chinese Ming Dynasty, there are special treatments like 導引按蹻法($d{\check{a}}o$ y ${\check{i}}n$ ${\grave{a}}n$ $ji{\check{a}}o$ $f{\check{a}}$), 搐鼻法($ch{\grave{u}}$ $b{\acute{i}}$ $f{\check{a}})$, 吐法($t{\check{u}}$ $f{\check{a}}$), 外貼法($w{\grave{a}}i$ $ti{\bar{e}}$ $f{\check{a}}$), 熨法($y{\grave{u}}n$ $f{\check{a}}$), 點眼法($di{\check{a}}n$ $y{\check{a}}n$ $f{\check{a}}$), 熏蒸法($x{\bar{u}}nzh{\bar{e}}ng$ $f{\check{a}}$), 香氣療法($xi{\bar{a}}ngq{\grave{i}}$ $li{\acute{a}}of{\check{a}}$). Most of this therapy in the treatment of headache, it is not used here, but if you use a good fit for today's environment can make a difference.

Sodium Salicylate(NaSaL) Induces Apoptosis of NCI-H1299 Lung Carcinoma Cells via Activation Caspase-3 Protease (NCI-H1299 폐암 세포주에서 Caspase-3 Protease 활성을 통한 Sodium Salicylate(NaSaL)의 세포고사)

  • Shim, Hyeok;Yang, Sei-Hoon;Bak, Sang-Myeon;Jeong, Eun-Taik
    • Tuberculosis and Respiratory Diseases
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    • v.53 no.5
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    • pp.485-496
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    • 2002
  • Background : Nonsteroidal anti-inflammatory drugs (NSAIDs) are useful in the chemoprevention of colon cancers. Continuous NSAID use results in a 40% to 50% reduction in the relative risk of colorectal cancer. The precise mechanism by which NSAIDs prevent and/or cause the regression of colorectal tumors is not known. Some investigators have reported that certain NSAIDs induce apoptosis and alter the expression of the cell cycle regulatory genes in some carcinoma cells when administered at a relatively high concentration. However, the possibility of NSAIDs application as chemopreventive agents in lung cancers remains to be elucidated. To address this question, the human lung cancer cell line NCI-H1299 was used to investigate whether or not NSAIDs might induce the apoptotic death of NCI-H1299 cells. Methods : A viability test was carried out using a MTT assay. Apoptosis was measured by flow cytometric analysis and unclear staining(DAPI). The talytic activity of the caspase family was measured by the fluirigenic cleavage of biosubstrates. To define the mechanical basis of apoptosis, western blot was performed to analyze the expression of the death substrates(PARP and ICAD). Results : NaSaL significantly decreased the viability of the NCI-H1299 cells, which was revealed as apoptosis characterized by an increase in the $subG_0/G_1$ population and unclear fragmentation. The catalytic activity of caspase-3 protease began to increase after 24 Hr and reached a peak 30 Hr after treatment with 10 mM NaSaL. In contrast, caspase-6, 8, and 9 proteases did not have a significantly altered enzymatic activity. Consistent with activation of caspase-3 protease, NaSaL induced the cleavage of the protease biosubstrate. Conclusion : NaSaL induces the apoptotic death of NCI-H1299 human lung cancer cells via the activation of caspase-3 protease.

Interrelationship between Dopaminergic Receptors and Catecholamine Secretion from the Rat Adrenal Gland (흰쥐 부신에서 카테콜아민 분비작용과 도파민 수용체간의 상관성)

  • Lim, Dong-Yoon;Yoon, Joong-Keun;Moon, Baek
    • The Korean Journal of Pharmacology
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    • v.30 no.1
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    • pp.87-100
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    • 1994
  • It has been known for some time that dopamine-containing cells are existed in sympathetic ganglia, i.e., small, intensely fluorescent cells. However, its role and mechanism of action as a peripheral neurotransmitter are poorly understood so far. In the present study, an attempt was made to examine the effect of apomorphine, which is known to be a selective agonist of dopaminergic $D_2$. receptor on secretion of catecholamines (CA) from the isolated perfused rat adrenal gland. The perfusion of a low concentration of 10uM apomorphine into an adrenal vein for 20 min produced significant reduction in CA secretion induced by 5.32 mM ACh, 56 mM KCl, 100 uM DMPP and 100 uM McN-A-343. Increasing apomorphine concentration to 30 uM led to more markedly decreased CA secretion as compared to the case of 10 uM apomorphine and also did inhibit clearly CA release by $10^{-5}M$ Bay-K-8644. Furthermore, in adrenal glands preloaded with a higher dose of 100 uM apomorphine, CA releases evoked by ACh, excess $K^+$, DMPP and McN-A-343 were almost abolished by the drug. The perfusion of $3.3{\pm}10^{-5}M$ metoclopramide, which is well-known as a selective dopaminergic $D_2$ antagonist, produced significantly inhibitory effect of CA release by ACh, DMPP and McN-A-343 but did not affect that by excess $K^+$. However, preloading of 30uM apomorphine in the presence of metoclopramide did not modify the CA secretory effect of excess $K+$ and DMPP. These experimental results demonstrate that apomorphine causes dose-dependent inhibition of CA secretion by cholinergic receptor stimulation and also by membrane depolarization from the isolated perfused rat adrenal gland, suggesting that these effects appear to be exerted by inhibiting influx of extracellular calcium into the rat adrenal medullary chromaffin cells through activation of inhibitory dopaminergic receptors.

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