• Title/Summary/Keyword: Modulating Effect

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RGS3 Suppresses cAMP Response Element (CRE) Activity Mediated by CB2 Cannabinoid Receptor in HEK293 Cells (캐너비노이드 수용체 CB2의 신호전달작용에 미치는 RGS3의 억제적 효과)

  • Kim, Sung-Dae;Lee, Whi-Min;Endale, Mehari;Cho, Jae-Youl;Park, Hwa-Jin;Oh, Jae-Wook;Rhee, Man-Hee
    • Journal of Life Science
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    • v.19 no.11
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    • pp.1506-1513
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    • 2009
  • RGS proteins have been identified as negative regulators of G protein signalling pathways and attenuate the activity of GPCR receptors. However, information on the regulatory effects of RGS proteins in the activity of cannabinoid receptors is limited. In this study, the role of RGS proteins on the signal transduction of the CB2 cannabinoid receptor was investigated in HEK293 cells co-transfected with CB2-receptors and plasmids encoding RGS2, RGS3, RGS4 and RGS5. Treatment of cells with WIN55, 212-2, a CB2 receptor agonist, inhibited forskolin-induced cAMP response element (CRE) activity in CB2-transfected HEK293 (CB2-HEK293) cells. This inhibitory effect of WIN 55, 212-2 on CRE activity was reversed by co-transfection of CB2-HEK293 cells with RGS3, but not with RGS2, RGS4 and RGS5. However, endogenous RGS3 protein knocked down by a small interfering siRNA targeting RGS3 gene enhanced inhibition of forskolin induced CRE activity via agonist induced CB2 receptor signal transduction. These results indicate the functional role of endogenous RGS protein in cannabinoid signaling pathways and define receptor-selective roles of endogenous RGS3 in modulating CRE transcriptional responses to agonist induced CB2 receptor activity.

Pectinase-treated Panax ginseng protects against chronic intermittent heat stress-induced testicular damage by modulating hormonal and spermatogenesis-related molecular expression in rats

  • Kopalli, Spandana Rajendra;Cha, Kyu-Min;Lee, Sang-Ho;Ryu, Ji-Hoon;Hwang, Seock-Yeon;Jeong, Min-Sik;Sung, Jong-Hwan;Kim, Si-Kwan
    • Journal of Ginseng Research
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    • v.41 no.4
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    • pp.578-588
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    • 2017
  • Background: Elevated testicular temperature disrupts spermatogenesis and causes infertility. In the present study, the protective effect of enzymatically biotransformed Panax ginseng Meyer by pectinase (GINST) against chronic intermittent heat stress-induced testicular damage in rats was investigated. Methods: Male Sprague-Dawley rats (4 wk old, 60-70 g) were divided into four groups: normal control (NC), heat-stress control (HC), heat-stress plus GINST-100 mg/kg (HG100), and heat-stress plus GINST-200 mg/kg (HG200) treatment groups. Each dose of GINST (100 mg/kg and 200 mg/kg) was mixed separately with a regular pellet diet and was administered orally for 24 wk. For inducing heat stress, rats in the NC group were maintained at $25^{\circ}C$, whereas rats in the HC, HG100, and HG200 groups were exposed to $32{\pm}1^{\circ}C$ for 2 h daily for 6 mo. At week 25, the testes and serum from each animal were analyzed for various parameters. Results: Significant (p < 0.01) changes in the sperm kinematic values and blood chemistry panels were observed in the HC group. Furthermore, spermatogenesis-related molecules, sex hormone receptors, and selected antioxidant enzyme expression levels were also altered in the HC group compared to those in the NC group. GINST (HS100 and HS200) administration significantly (p < 0.05) restored these changes when compared with the HC group. For most of the parameters tested, the HG200 group exhibited potent effects compared with those exhibited by the HG100 group. Conclusion: GINST may be categorized as an important medicinal herb and a potential therapeutic for the treatment of male subfertility or infertility caused by hyperthermia.

Insulin-like Growth Factor-I Induces Plectin and MACF1 Expression in C2C12 Myotubes (C2C12 myotube에서 insulin-like growth factor-I이 plectin과 MACF1 발현에 미치는 영향)

  • Kim, Hye Jin;Hwang, Ji Sun;Kwak, Yi-Sub;Lee, Won Jun
    • Journal of Life Science
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    • v.22 no.12
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    • pp.1651-1657
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    • 2012
  • Plectin and microtubule actin cross-linking factor 1 (MACF1) are architectural proteins that contribute to the function of skeletal muscle as generators of mechanical force. However, the influence of insulin- like growth factor-I (IGF-I), a master regulator of skeletal muscle cells, on plectin and MACF1 in skeletal muscle cells has not been demonstrated. The effect of IGF-I on plectin and MACF1 gene expression was investigated by treating differentiated C2C12 murine skeletal muscle cells with 20 ng/ml of IGF-I at different time points. The IGF-I treatment increased plectin protein expression in a dose-dependent manner. The mRNA level of plectin was measured by real-time quantitative PCR to determine if plectin induction was regulated pretranslationally. IGF-I treatment resulted in a very rapid induction of plectin mRNA transcript in C2C12 myotubes. Plectin mRNA increased by 140 and 180% after 24 and 48 hours of IGF-I treatment, respectively, and returned to the control level after 72 hours of IGF-I treatment. MACF1 mRNA increased 86 and 90% after 24 and 48 hours of IGF-I treat-ment, respectively, and returned to the control level after 72 hours of IGF-I treatment. These results suggested that the plectin gene is regulated pretranslationally by IGF-I in skeletal muscle cells. In conclusion, IGF-I induces a rapid transcriptional modification of the plectin and MACF1 genes in C2C12 skeletal muscle cells and has modulating effects on a cytolinker protein as well as on contractile proteins.

Inhibition of Migration and Invasion of LNCap Human Prostate Carcinoma Cells by Doxorubicin through Inhibition of Matrix Metalloproteinase Activity and Tightening of Tight Junctions (Doxorubicin에 의한 치밀결합 강화 및 MMPs의 활성 억제를 통한 LNCap 전립선 암세포의 이동성 및 침윤성의 억제)

  • Choi, Yung Hyun;Shin, Dong Yeok;Kim, Wun-Jae
    • Journal of Life Science
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    • v.24 no.6
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    • pp.700-706
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    • 2014
  • Doxorubicin (trade name adriamycin), an anthracycline antibiotic, is commonly used in the treatment of a wide range of cancers, including hematological malignancies, many types of carcinoma, and soft tissue sarcomas. It is closely related to the natural product daunomycin, and like all anthracyclines, it works by intercalating DNA. Its most serious adverse effect is life-threatening heart damage. Its anti-metastatic mechanisms in human prostate carcinomas are not fully understood. In this study, we used LNCap human prostate carcinoma cells to investigate the inhibitory effects of doxorubicin on cell motility and invasion, two critical cellular processes that are often deregulated during metastasis. Doxorubicin treatment inhibited cell migration and invasiveness of LNCap cells without showing any toxicity. Doxorubicin treatment also suppressed the activity and expression of matrix metalloproteinase (MMP)-2 and MMP-9, which were associated with up-regulated expression of tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 in LNCap cells. Doxorubicin treatment also attenuated the expression levels of claudin family members (claudin-1, -2,-3 and -4), major components of tightening of tight junctions (TJs) and increased the tightening of TJs, as demonstrated by an increase in transepithelial electrical resistance. The present findings demonstrate that doxorubicin reduces the migration and invasion of prostate carcinomas LNCap cells by modulating the activity of TJs and MMPs.

Skin Whitening and Skin Immune Activities of Different Parts of Acer mono and Acer okamotoanum (고로쇠 및 우산고로쇠나무의 부위별 미백 및 피부면역 활성)

  • Jeong, Myoung-Hoon;Kim, Seung-Seop;Kim, Ji-Seon;Lee, Hak-Ju;Chio, Geun-Pyo;Lee, Hyeon-Yong
    • Journal of Korean Society of Forest Science
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    • v.99 no.4
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    • pp.470-478
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    • 2010
  • UV-protection skin whitening and immune activities several parts of Acer mono and Acer okamotoanum were investigated. The bark of both Acer mono and Acer okamotoanum had higher yields than other parts as 2.67% and 2.45%. The cytotoxicity of the extracts were lower than 21.64% against human skin cell(CCD-986sk) line in adding 1.0 mg/mL of the highest concentration. The bark extracts of Acer mono greatly reduced the expression of MMP-1 on UV-irradiated CCD-986sk cells down to as 30%. At 1.0 mg/mL of bark extration of Acer mono, $PGE_2$ expression was also significantly decreased. Generally, the bark extracts of Acer mono and Acer okamotoanum had higher activity than other parts, but, interestingly, wood extract of Acer okamotoanum showed strong inhibition effect on melanin production by Clone-M3 cells as 79.25%. From these results, we could conclude that the bark extract from Acer mono and Acer okamotoanum had skin-whitening activity as well immune enhancement activity.

The Comparison of Extraction Process for Enhancement of Immunomodulating Activities of Ulva pertusa kjellman (구멍갈파래의 면역활성 증진을 위한 추출방법 비교)

  • Han, Jae-Gun;Ha, Ji-Hye;Choi, Yeong-Beom;Go, Jeong-Lim;Kang, Do-Hyung;Lee, Hyeon-Yong
    • Korean Journal of Food Science and Technology
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    • v.41 no.4
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    • pp.380-385
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    • 2009
  • The purpose of this study was to investigate the immunomodulatory effect of Ulva pertusa kjellman extract after undergoing a low temperature and high-pressure extraction process. First, the extracts obtained under the extraction conditions of 150 MPa and $80^{\circ}C$showed a relatively high antioxidant activity, with 90% super oxide radical activity compared to the extracts from conventional extraction process with water at $100^{\circ}C$. This extract also improved the growth of both human immune B and T cells up to $14.5{\times}10^4$ cells/mL and $14.2{\times}10^4$ cells/mL compared to $9.1{\times}10^4$ cells/mL in adding the extracts from conventional processes. It was found that the extracts obtained at 100 MPa and $60^{\circ}C$ showed better activities in NK cell growth and NO production from macrophage as $11.8{\times}10^2$ cells/mL and 30.0 ${\mu}M$. Overall, the extracts from high pressure and low temperature extraction process had relatively higher immune activation activity, possibly because the low temperature and high pressure extraction process may have higher yields of active compounds and have less damage to useful ingredients from relatively weak marine natural resources, such as Ulva pertusa kjellmann than that from the conventional extraction system.

Inhibitory Effects of Allium senescens L. Methanol Extracts on Reactive Oxygen Species Production and Lipid Accumulation during Differentiation in 3T3-L1 Cells (두메부추(Allium senescens L.) 메탄올 추출물의 지방세포 내 활성산소종 생성 및 지질축적 억제 효능)

  • Choi, Hye-Young;Kim, Gun-Hee
    • Korean Journal of Food Science and Technology
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    • v.46 no.4
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    • pp.498-504
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    • 2014
  • Allium senescens L. is perennial plant of the Liliaceae family that grows throughout Korea. In this study, we investigated the effect of Allium senescens L. methanol extracts on reactive oxygen species (ROS) production and lipid accumulation during adipogenesis. Our results indicated that 1,1-diphenyl-2-picrylhydrazyl radical scavenging activity of Allium senescens L. methanol extracts increased in a dose-dependent manner. Allium senescens L. methanol extracts suppressed ROS production and lipid accumulation during adipogenesis. In addition, Allium senescens L. methanol extracts inhibited the mRNA expression of the pro-oxidant enzyme, such as G6PDH and lead to a reduction in the mRNA levels of the transcription factors, such as sterol regulatory element binding proteins 1c, peroxisome proliferator-activated receptor ${\gamma}$, and CCAAT/enhancer-binding proteins ${\alpha}$. These results indicate that Allium senescens L. methanol extracts inhibit adipogenesis by modulating ROS production associated with ROS-regulating genes and directly down-regulating adipogenic transcription factors.

The Effect of Mineral Trioxide Aggregate on the Production of Growth Factors and Cytokine by Human Periodontal Ligament Fibroblasts (Mineral trioxide aggregate (MTA)가 치주인대 섬유아세포에서 분비되는 cytokine과 성장인자 TGF-β1, FGF-2 발현에 미치는 영향)

  • Kwon, Ji-Yoon;Lim, Sung-Sam;Baek, Seung-Ho;Bae, Kwang-Shik;Kang, Myung-Hoe;Lee, Woo-Cheol
    • Restorative Dentistry and Endodontics
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    • v.32 no.3
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    • pp.191-197
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    • 2007
  • Mineral trioxide aggregate (MTA) would influence healing of periapical tissues by modulating the production of growth factors and cytokines from PDL fibroblasts, however, the studies are insufficient. Therefore, the purpose of this study was to monitor the expression of transforming growth factor-beta1 $(TGF-\beta1)$, fibroblast growth factor-2 (FGF-2), and interleukin-6 (IL-6) from PDL fibroblasts in the presence of MTA. The human PDL fibroblasts were seeded onto the set MTA or IRM at a level of $1\times10^5$ cells per unit well, and further incubated for 6, 12, 24, and 48 hours. The levels of $TGF-\beta1$, FGF-2 and IL-6 from the supernatant were measured by enzyme-linked immunosorbent assay (ELISA) The data were analyzed using one-way ANOVA. The level of $TGF-\beta1$ was down-reg ulated when the cells were grown in the presence of MTA except at 6 hours. The levels of FGF-2 release were significantly suppressed when PDL fibroblasts were grown in the presence of MTA or IRM at all time intervals (p < 0.05). The expressions of IL-6 from MTA treated co)Is were comparable to those of untreated control cells throughout the observation periods. We presume that this material inhibits the stimulatory function of growth factors on granulation tissue formation and in turn, it promotes the healing process modulated by other bone-remodeling cells.

Effects of Cudrania Tricuspidata Root Extract (CTE) on Ethanol-Induced Hangover via Modulating Alcohol Metabolizing Enzyme Activities and Blood Gas Levels in Rats (꾸지뽕나무 뿌리 추출물의 알코올 대사 효소 활성 및 혈액 산성화 기전 조절을 통한 숙취해소 효과)

  • Choi, Na-Eun;Ro, Ju-Ye;Lee, Ju-Yeong;Ryu, Jin-Hyeob;Cho, Hyun-Jeong
    • Journal of the Korea Academia-Industrial cooperation Society
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    • v.18 no.2
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    • pp.218-225
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    • 2017
  • To investigate the anti-hangover effects of Cudrania tricuspidata root extract (CTE), the blood alcohol metabolism and blood gas imbalance of CTE in rats treated with 10 ml/kg alcohol were examined. CTE (500 mg/kg and 750 mg/kg) was administrated after 30 minutes of alcohol consumption (10 ml/kg). Blood collection was implemented from the tails of the animals after 1, 3, and 5 hours post alcohol consumption. The Condition drink (a commercial anti-hangover beverage) was used as a positive control. Single administration by the oral route was performed. The consumption of CTE (500 mg/kg and 750 mg/kg) decreased the serum alcohol concentration by increasing and maintaining both the alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH) enzyme activity levels in the blood and liver. In addition, CTE led to recovery from the imbalances in the blood gas levels, including carbon dioxide ($CO_2$) and changes in pH, bicarbonate ($HCO_3{^-}$) and lactic acid levels due to alcohol ingestion. In conclusion, CTE exerted a more pronounced anti-hangover effect than a commercial anti-hangover drink. Therefore, CTE can be a novel and safe anti-hangover natural product agent for the prevention or treatment of symptoms caused by excessive alcohol consumption.

Recent advances on next-generation probiotics linked to the gut microbiome (장내 마이크로바이옴과 차세대 프로바이오틱스 연구 현황)

  • Choi, Hak-Jong
    • Food Science and Industry
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    • v.52 no.3
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    • pp.261-271
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    • 2019
  • Gut microbiome have recently provided evidence that the gut microbiota are capable of greatly influencing all aspects of physiology and immunology. Although a number of recent studies have shown that probiotics can modulate gut microbiota structure, the mechanism underlying this effect remains to be elucidated. In a disease state, the relative abundances of beneficial gut bacteria are generally reduced, which is restored by constant probiotic supplementation. Oral administration of probiotics improved the disease state by (1) inducing differentiation and function of regulatory T cells, (2) reducing inflammatory response, (3) modulating the gut environment, and (4) increasing the proportions of short-chain fatty acid- or beneficial metabolite-producing gut microbiota including the genera Bifidobacterium, Faecalibacterium, Akkermansia, etc. In this review, current knowledge on how probiotics can influence host's health by altering gut microbiota structure and on how probiotics and beneficial gut bacteria can be applied as next-generation probiotics will be discussed.