• 제목/요약/키워드: Protein phosphatase 2A

검색결과 518건 처리시간 0.035초

Melanin extract from Gallus gallus domesticus promotes proliferation and differentiation of osteoblastic MG-63 cells via bone morphogenetic protein-2 signaling

  • Yoo, Han-Seok;Chung, Kang-Hyun;Lee, Kwon-Jai;Kim, Dong-Hee;An, Jeung Hee
    • Nutrition Research and Practice
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    • 제11권3호
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    • pp.190-197
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    • 2017
  • BACKGROUND/OBJECTIVES: Gallus gallus domesticus (GD) is a natural mutant breed of chicken in Korea with an atypical characterization of melanin in its tissue. This study investigated the effects of melanin extracts of GD on osteoblast differentiation and inhibition of osteoclast formation. MATERIALS/METHODS: The effects of the melanin extract of GD on human osteoblast MG-63 cell differentiation were examined by evaluating cell viability, osteoblast differentiation, and expression of osteoblast-specific transcription factors such as bone morphogenetic protein 2 (BMP-2), small mothers against decapentaplegic homologs 5 (SMAD5), runt-related transcription factor 2 (RUNX2), osteocalcin and type 1 collagen (COL-1) by reverse transcription-polymerase chain reaction and western blotting analysis. We investigated the inhibitory effect of melanin on the osteoclasts formation through tartrate-resistant acid phosphatase (TRAP) activity and TRAP stains in Raw 264.7 cell. RESULTS: The melanin extract of GD was not cytotoxic to MG-63 cells at concentrations of $50-250{\mu}g/mL$. Alkaline phosphatase (ALP) activity and bone mineralization of melanin extract-treated cells increased in a dose-dependent manner from 50 to $250{\mu}g/mL$ and were 149% and 129% at $250{\mu}g/mL$ concentration, respectively (P < 0.05). The levels of BMP-2, osteocalcin, and COL-1 gene expression were significantly upregulated by 1.72-, 4.44-, and 2.12-fold in melanin-treated cells than in the control cells (P < 0.05). The levels of RUNX2 and SMAD5 proteins were higher in melanin-treated cells than in control vehicle-treated cells. The melanin extract attenuated the formation of receptor activator of nuclear factor kappa-B ligand-induced TRAP-positive multinucleated RAW 264.7 cells by 22%, and was 77% cytotoxic to RAW 264.7 macrophages at a concentration of $500{\mu}g/mL$. CONCLUSIONS: This study provides evidence that the melanin extract promoted osteoblast differentiation by activating BMP/SMADs/RUNX2 signaling and regulating transcription of osteogenic genes such as ALP, type I collagen, and osteocalcin. These results suggest that the effective osteoblastic differentiation induced by melanin extract from GD makes it potentially useful in maintaining bone health.

Emodin stimulates the osteoblast differentiation via activating bone morphogenetic protein-2 gene expression at low concentration

  • Cheon, Myeong-Sook;Lee, Su-Ui;Kim, Ho-Kyoung;Kim, Young-Sup;Min, Yong-Ki;Kim, Seong-Hwan
    • 한국한의학연구원논문집
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    • 제13권1호통권19호
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    • pp.139-145
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    • 2007
  • Emodin is one of the main active components of a traditional Korean medicine isolated from the root and rhizomes of Rheum palmatum L. In this study, of 222 natural compounds to evaluate the anabolic activities, emodin activated bone morphogenetic protein (BMP)-2 promoter in the differentiation process of mouse osteoblastic MC3T3-E1 cells. Emodin was shown to significantly stimulate the activity and expression of alkaline phosphatase, an earlyphase marker of osteoblastic differentiation, on the differentiation day 7, and induce the osteopontin mRNA expression from the differentiation day 14. In addition, low concentration (up to 5 M) of emodin dramatically promoted the induction of mineralization in MC3T3-E1 subclone 4 cells. The stimulatory effect of emodin on the osteoblast differentiation/mineralization could be associated with its potential to stimulate the BMP-2 gene expression. Although further studies are needed to determine the precise mechanism, this study suggests that the use of herbal medicine containing natural compounds with anabolic activity such as emodin could have a beneficial effect on bone health.

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고지방식이 유발 제2형 당뇨모델 마우스에서 작약의 혈당강하 효능 (Hypoglycemic Effect of Paeonia lactiflora in High Fat Diet-Induced Type 2 Diabetic Mouse Model)

  • 윤인수;정유정;김현정;임현진;조승식;심정현;강복윤;천승훈;김수남;윤구
    • 생약학회지
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    • 제45권3호
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    • pp.194-199
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    • 2014
  • The roots of Paeonia lactiflora (PL) has been traditionally used as analgesic, spasmolytic and tonic in Korea, China, and Japan. As part of a search for herbal medicine to treat diabetes and obesity, we confirmed hypoglycemic effect of PL through high fat diet-induced obese and diabetic mice experiments in vivo. Treatment of ethanolic extract from PL led to a significant decrease in glucose level, which is comparable to that of an antidiabetic drug metformin. In addition, PL selectively stimulates the transcriptional activities of both peroxisome proliferator-activated receptor $(PPAR){\alpha}$ and ${\gamma}$, and inhibits enzymatic activity of protein tyrosine phosphatase 1B (PTP1B), which are predicted to be therapeutic target in treatment of type2 diabetes and obesity. Especially, the n-hexane fraction (Hx) from PL ethanol extract showed more potent activities on $PPAR{\alpha}$ and than others and exihibited moderate inhibitory activity against PTP1B.

B형 간염 항원 양성 및 간효소치가 증가된 환자에 Enflurane 마취가 간에 미치는 영향 (The Effect of Enflurane Anesthesia on The Liver in patient with posilive HBsAg and increased SGOT, SGPT)

  • 서일숙;박대팔
    • Journal of Yeungnam Medical Science
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    • 제7권1호
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    • pp.121-126
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    • 1990
  • 전신마취를 필요로 하는 무증상 HBsAg양성 간효소치가 증가된 환자 11명을 대상으로 enflurane으로 마취한후 술전, 술후 3일, 7일 및 10일에 간기능검사를 실시하여 그 변화를 비교 검사한 결과 다음과 같은 결론을 얻었다. 1) SGOT, SGPT SGOT, SGPT는 술후 3일에는 술전수치보다 약간 증가하였으나 7일, 10일에는 현저한 증가를 보였다. 8예에 있어서는 술후 3일에 술전치 보다 약간 증가한 양상을 보였고 7일, 10일에 술전치와 비슷하게 되었으나 3예에서는 3일에 SGOT, SGPT가 약간 증가하더니 7일, 10일에는 SGOT, SGPT가 300-500IU로 상당히 증가하여 간염치료를 하여 술후 2개월후에 술전치와 비슷하게 하강하였다. 2) Alkaline phosphatase, total protein, albumin, total bilirubin, and direct bilirubin은 술후 3일에 정상범위를 벗어난 변화를 보였으며 7일부터 정상범위내로 회복되었다. 이상의 결과를 보아 enflurane마취가 간기능에 큰 영향을 미치지 않는다고는 하나 HBaAg양성 간효소치가 증가한 환자에게는 마취시 간염으로 이행될 가능성이 높으므로 상당히 조심을 하여 마취를 시행하여야 할 것으로 사료된다.

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Impact of transgenic AFPCHI (Cucumis melo L. Silver Light) fungal resistance melon on soil microbial communities and enzyme activities

  • Bezirganoglu, Ismail;Uysal, Pinar
    • Journal of Plant Biotechnology
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    • 제44권2호
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    • pp.156-163
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    • 2017
  • A greenhouse experiment was conducted for evaluation of ecological effects of transgenic melon plants in the rhizospheric soil in terms of soil properties, enzyme activities and microbial communities. Organic matter content of soil under transgenic melon plants was significantly higher than that of soil with non-transgenic melon plants. Significant variations were observed in organic matter, total P and K in soil cultivation with transgenic melon plants. There were also significant variations in the total numbers of colony forming units of fungi, actinomycetes and bacteria between soils treated with transgenic and non-transgenic melon plants. Transgenic and non-transgenic melon significantly enhanced several enzymes activities including urease, acid phosphatase, alkalin phosphatase, arysulphtase, ${\beta}$ glucosidase, dehydrogenase, protease and catalase. Soil polyphenoloxidase activity of $T_1$ transgenic melon was lower than that of $T_0$ transgenic melon and a non-melon plant during the same period. The first generation transgenic melon plants ($T_0$) showed significantly greater (p<0.05) effect on the activitiy of arylsulfatase, which increased from $2.540{\times}10^6CFU\;g^{-1}$ (control) to $19.860{\times}10^6CFU\;g^{-1}$ ($T_0$). These results clearly indicated that transgenic melon might change microbial communities, enzyme activities and soil chemical properties.

난소를 절제한 나이가 다른 흰쥐에서 식이 칼슘 수준이 골격 대사에 미치는 영향 (The Effects of Dietary Ca Levels on Ca and Skeletal Metabolism in Ovariectomized Rats of Different Age)

  • 김화영
    • Journal of Nutrition and Health
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    • 제31권4호
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    • pp.716-728
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    • 1998
  • To investigate the effect of dietary Ca levels on metabolic changes of Ca and skeleton in postmenopausal women, 10-month-old ovariectomized female rats were compared with 2 month old rats. The rats were fed either 0.2% or 1.2% Ca diets for 16 weeks. Food intake and weight gain as higher in rats fed high Ca diets and in ovariectomized rats. Apparent Ca absorption as higher, and Ca balance was lower in the low Ca groups. Vertebrae density was higher in old rats or those fed a high Ca diets. The old rats and ovariectomized rats showed decreased bone formation, increased bone resorption and kidney function deterioration resulting in increased urinary Ca excretion. Contradictory to the above observation, old rats and ovariectomized rats still showed higher bone mass and bone ash content. Therefore aging was not fully onging in 10-month-old rats. Bone weights, mineral contents, and mineral/wt ratio were lower in ovariectomized rats. Dietary Ca level did not affect urinary Ca excretion, urinary protein excretion, GFR, serum alkaline phosphatase, or urinary hydroxyporline excretion. This means that dietary Ca level did not influence kidney function or bone turnover. However Ca content and the ash content of femur, 4th vertebra, and scapula were increased in high Ca groups. Therefore, it is considered that decreased bone formation and accelerated bone resorption may account for the increased osteoporotic risk in women in menopause after middle age. However, Ca metabolism can be improved and bone components can be maintained if Ca is supplemented.

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Changes of Gene Expression in NIH3T3 Cells Exposed to Osmotic and Oxidative Stresses

  • Lee, Jae-Seon;Jung, Ji-Hun;Kim, Tae-Hyung;Seo, Jeong-Sun
    • Genomics & Informatics
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    • 제2권2호
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    • pp.67-74
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    • 2004
  • Cells consistently face stressful conditions, which cause them to modulate a variety of intracellular processes and adapt to these environmental changes via regulation of gene expression. Hyperosmotic and oxidative stresses are significant stressors that induce cellular damage, and finally cell death. In this study, oligonucleotide microarrays were employed to investigate mRNA level changes in cells exposed to hyperosmotic or oxidative conditions. In addition, since heat shock protein 70 (HSP70) is one of the most inducible stress proteins and plays pivotal role to protect cells against stressful condition, we performed microarray analysis in HSP70-overexpressing cells to identify the genes expressed in a HSP70-dependent manner. Under hyperosmotic or oxidative stress conditions, a variety of genes showed altered expression. Down­regulation of protein phosphatase1 beta (PP1 beta) and sphingosine-1-phosphate phosphatase 1 (SPPase1) was detected in both stress conditions. Microarray analysis of HSP70-overexpressing cells demonstrated that diverse mRNA species depend on the level of cellular HSP70. Genes encoding Iysyl oxidase, thrombospondin 1, and procollagen displayed altered expression in all tested conditions. The results of this study will be useful to construct networks of stress response genes.

Activation of G Proteins by Aluminum Fluoride Enhances RANKL-Mediated Osteoclastogenesis

  • Park, Boryung;Yang, Yu-Mi;Choi, Byung-Jai;Kim, Min Seuk;Shin, Dong Min
    • The Korean Journal of Physiology and Pharmacology
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    • 제17권5호
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    • pp.427-433
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    • 2013
  • Receptor activator of NF-${\kappa}B$ ligand (RANKL)-induced osteoclastogenesis is accompanied by intracellular $Ca^{2+}$ mobilization in a form of oscillations, which plays essential roles by activating sequentially $Ca^{2+}$/calmodulin-dependent protein kinase, calcineurin and NFATc1, necessary in the osteoclast differentiation. However, it is not known whether $Ca^{2+}$ mobilization which is evoked in RANKL-independent way induces to differentiate into osteoclasts. In present study, we investigated $Ca^{2+}$ mobilization induced by aluminum fluoride ($AlF_4^-$), a G-protein activator, with or without RANKL and the effects of $AlF_4^-$ on the osteoclastogenesis in primary cultured mouse bone marrow-derived macrophages (BMMs). We show here that $AlF_4^-$ induces intracellular $Ca^{2+}$ concentration ($[Ca^{2+}]_i$) oscillations, which is dependent on extracellular $Ca^{2+}$ influx. Notably, co-stimulation of $AlF_4^-$ with RANKL resulted in enhanced NFATc1 expression and formation of tartrate-resistant acid phosphatase (TRAP) positive multinucleated cells. Additionally, we confirmed that mitogen-activated protein kinase (MAPK) is also activated by $AlF_4^-$. Taken together, these results demonstrate that G-protein would be a novel modulator responsible for $[Ca^{2+}]_i$ oscillations and MAPK activation which lead to enhancement of RANKL-mediated osteoclastogenesis.

Anti-oxidative Effect of a Protein from Cajanus indicus L against Acetaminophen-induced Hepato-nephro Toxicity

  • Ghosh, Ayantika;Sil, Parames C.
    • BMB Reports
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    • 제40권6호
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    • pp.1039-1049
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    • 2007
  • Overdoses of acetaminophen cause hepato-renal oxidative stress. The present study was undertaken to investigate the protective effect of a 43 kDa protein isolated from the herb Cajanus indicus, against acetaminophen-induced hepatic and renal toxicity. Male albino mice were treated with the protein for 4 days (intraperitoneally, 2 mg/kg body wt) prior or post to oral administration of acetaminophen (300 mg/kg body wt) for 2 days. Levels of different marker enzymes (namely, glutamate pyruvate transaminase and alkaline phosphatase), creatinine and blood urea nitrogen were measured in the experimental sera. Intracellular reactive oxygen species production and total antioxidant activity were also determined from acetaminophen and protein treated hepatocytes. Indices of different antioxidant enzymes (namely, superoxide dismutase, catalase, glutathione-S-transferase) as well as lipid peroxidation end-products and glutathione were determined in both liver and kidney homogenates. In addition, Cytochrome P450 activity was also measured from liver microsomes. Finally, histopathological studies were performed from liver sections of control, acetaminophen-treated and protein pre- and post-treated (along with acetaminophen) mice. Administration of acetaminophen increased all the serum markers and creatinine levels in mice sera along with the enhancement of hepatic and renal lipid peroxidation. Besides, application of acetaminophen to hepatocytes increased reactive oxygen species production and reduced the total antioxidant activity of the treated hepatocytes. It also reduced the levels of antioxidant enzymes and cellular reserves of glutathione in liver and kidney. In addition, acetaminophen enhanced the cytochrome P450 activity of liver microsomes. Treatment with the protein significantly reversed these changes to almost normal. Apart from these, histopathological changes also revealed the protective nature of the protein against acetaminophen induced necrotic damage of the liver tissues. Results suggest that the protein protects hepatic and renal tissues against oxidative damages and could be used as an effective protector against acetaminophen induced hepato-nephrotoxicity.