Glucose Controls the Expression of Polypyrimidine Tract-Binding Protein 1 via the Insulin Receptor Signaling Pathway in Pancreatic β Cells

정다은,허성은,한지혜,이은영,Rohit N. Kulkarni,김욱 한국분자세포생물학회 2018 Molecules and cells Vol.41 No.10

In pancreatic β cells, glucose stimulates the biosynthesis of insulin at transcriptional and post-transcriptional levels. The RNA-binding protein, polypyrimidine tract-binding protein 1 (PTBP1), also named hnRNP I, acts as a critical mediator of insulin biosynthesis through binding to the pyrimidine-rich region in the 3’-untranslated region (UTR) of insulin mRNA. However, the underlying mechanism that regulates its expression in β cells is unclear. Here, we report that glucose induces the expression of PTBP1 via the insulin receptor (IR) signaling pathway in β cells. PTBP1 is present in β cells of both mouse and monkey, where its levels are increased by glucose and insulin, but not by insulin-like growth factor 1. PTBP1 levels in immortalized β cells established from wild-type (βIRWT) mice are higher than levels in β cells established from IR-null (βIRKO) mice, and ectopic re-expression of IR-WT in βIRKO cells restored PTBP1 levels. However, PTBP1 levels were not altered in βIRKO cells transfected with IR-3YA, in which the Tyr1158/1162/1163 residues are substituted with Ala. Consistently, treatment with glucose or insulin elevated PTBP1 levels in βIRWT cells, but not in βIRKO cells. In addition, silencing Akt significantly lowered PTBP1 levels. Thus, our results identify insulin as a pivotal mediator of glucose-induced PTBP1 expression in pancreatic β cells.

β(1-3)-D-glucan affects adipogenesis, wound healing and inflammation

Vaclav Vetvicka,Jana Vetvickova 경희대학교 융합한의과학연구소 2011 Oriental Pharmacy and Experimental Medicine Vol.11 No.3

Numerous types of β(1-3)-D-glucans have been isolated from almost every species of yeast, grain, and fungi. These products have been extensively studied for their immunological and pharmacological effects. In this paper we evaluated the possibility whether individual β(1-3)-D-glucans will have an activity in less studied areas such as adipogenesis and inflammation. Our results showed that of the tested β(1-3)-D-glucans, yeast-derived insoluble Glucan #300, strongly inhibited adipogenic differentiation,supported wound healing and significantly lowered skin irritation. The remaining β(1-3)-D-glucans were significantly less active. Taken together, our study showed that with respect to natural β(1-3)-D-glucans, there is a clear yes-or-no effect suggesting that highly purified and highly active β(1-3)-D-glucans will have pleiotropic biological impact, whereas poorly isolated and/or less active β(1-3)-D-glucans will have only mediocre properties.

β₁/β₂ 비선택적 Radioligand (-)-[³H]-DHA를 사용한 Rat 좌심실 β-adrenoceptor에 대한 심장순환계 약물의 Binding

권광일(Kwang-Il Kwon),이선경(Sun-Kyung Lee),유성은(Sung-Eun Yoo) 대한약리학회 1991 대한약리학잡지 Vol.27 No.2

β-수용체 효능약물 ((-)-NE), 길항약물 ((\pm)-propranolol, labetalol) 및 PDE 억제약물(imazodan, KR-30045, KR-30075 등)에 대한 β-adrenoceptor binding 실험을 β₁/β₂ 비선택적 radioligand인 (-)-[³H]-DHA를 사용하여 실시하였다. Saturation 실험에서 β_1 및 β_2 수용체를 모두 갖고 있는 rat 좌심실의 β 수용체에 대한 (-)-[³H]-DHA의 K_D 값은 1.5 ± 0.43 nM, B_{max}는 22.0 ± 0.9 fmol/mg protein이었다. ( ± )propranolol, labetalol 및 (-)NE는 단일상으로 (-)-[³H]-DHA의 결합을 억제하였으며 Ki 값은 각각 17.0 ± 0.43 nM, 57.3 ± 1.30 nM, 1.57 ± 0.95μM로 나타났다. 실험에 사용한 모든 PDE 억제약물들은 (-)-[³H]-DHA 결합을 10^-3 M의 고농도에서도 10% 미만으로 억제했다. 실험결과, propraolol, labetalol 및 NE는 β₁/β₂ 수용체에 대해 비선택적인 약물로 나타났으며, imazodan 및 신합성 PDE 억제약물들은 rat 심근에 있는 β-수용체에 친화성이 거의 없음을 알 수 있었다. β-adrenoceptor binding study of β-agonist ((-)NE), β-antagonists (( ± ) propranolol, labetalol) and PDE inhibitors (imazodan, KR-30045, KR-30075 etc.) was performed using (-)-[³H]-DHA, as a non-β₁/β₂ selective radioligand. In saturation studies, K_D and B_{max} of (-)-[³H]-DHA to β-adrenoceptors in rat left ventricle in which both β_1 and β_2 receptors coexist were determined to be 1.5 ± 0.43 nM and 22.0 ± 0.9 fmol/mg protein, respectively. ( ± )Propranolol, labetalol and (-)NE competed for (-)-[³H]-DHA binding sites in an essentialy monophasic manner with Ki=17.0 ± 0.40 nM, 57.3 ± 1.30 nM, and 1.57 ± 0.95μM, respectively. All of PDE inhibitors inhibited the (-)-[³H]-DHA binding by only below 10% even at the high concentration of 10^-3M. The present results suggest that propranolol, labetalol and NE are non-β₁/β₂ selective antagonists and agonist, respectively. Additionally, this study shows that imazodan and new synthesized PDE inhibitors may hardly have the affinities to β-adrenoceptors in cardiac muscle.

Some recurrence relations for the Jacobi polynomials Pn(α,β)(x)

최준상,Shine Raj S.N.,A. K. Rathie 영남수학회 2015 East Asian mathematical journal Vol.31 No.1

We use some known contiguous function relations for 2F1 toshow how simply the following three recurrence relations for Jacobi polynomials Pn(α,β)(x): (i) (α+β+n)Pn(α,β)(x)=(β+n)Pn(α,β-1)(x)+(α+n)Pn(α-1,β)(x); (ii) 2Pn(α,β)(x)=(1+x)Pn((α,β+1)(x)+(1-x)Pn((α+1,β)}(x); (iii)Pn-1(α,β)(x)=Pn(α,β-1)(x)+Pn(α-1,β)(x) can be established.

Interleukin-1β induces bone resorption by regulation of prostaglandin E₂ synthesis and plasminogen activator activity, and TGF-β inhibits bone resorption of rat bone cells

Kim, Young-Hun,Lee, Young-Jun,Chung, Kyu-Rhim,Park, Young-Guk 대한치과교정학회 2000 대한치과교정학회지 Vol.30 No.6

골세포는 골대사에 영향을 미치는 다양한 성장인자와 싸이토카인을 생성하여 골 기질로 유리시킨다. 이 연구는 쥐의 장골 세포 배양 모델에서 recombinant human IL-1β가 PGE2 합성과 plasminogen activator의 활성 조절을 통한 골흡수 유도 기전의 일단을 구명하고, 이와 동시에 TGF-β에 의한 골흡수 억제 기전을 해명하는데 그 목적이 있다. 쥐의 장골 세포를 배양하여 통법의 골모세포 phenotype을 발현하는 세포를 분리하고 세포 배양능, alkaline phosphatase assay, PG assay, 골흡수능 측정들을 시행하여 다음의 결과를 얻었다. 1.IL-1β는 쥐의 골모세포의 증식, PGE2 생성 및 palsmonogen activator의 활성을 촉진하였다. 2.IL-1β는 쥐의 골모세포에서의 alkaline phosphatase 활성을 감소시켰다. 3.rhIL-1β는 골 흡수를 촉진시켰다. 4.TGF-β는 쥐의 장골 세포에서 골의 흡수를 억제하였으며, Vitamin D3에 의하여 유도된 골 흡수를 억제하였다. 이상의 연구 결과는 IL-1β에 의한 골 파괴의 병인과 관련하여 골 세포 대사의 병리학적 조절에 있어서의 IL-1β의 역할을 지지하며, 이와 동시에 골 흡수 억제에 있어서의 TGF-β의 역할을 확인시켜주는 것으로 생각된다. Bone cells produce multiple growth factors and cytokines that hale effects on bone metabolism and can be incorporated into the bone matrix. The present study was designed to extend these observations by examining the interactions between transforming growth factor-β (TGF-β) or interleukin-1β (rhIL-1β) and bone cells in a rat long bone culture model. IL-1β regulates several activities of the osteoblast cells derived from rat long bone explants in vitro. IL-1β stimulated cellular proliferation as well as the synthesis of prostaglandin E2 and plasminogen activator activity in the cultured cells in a dose-dependent manner. TGF-β is present in the bone matrix and potentially released during bone resorption. TGF-β reduced basal bone resorption and inhibited vitamin D3 [1,25(OH)2D3]-Induced bone resorption in rat long bone cells. These results support the role of IL-1β in the pathological modulation of bone cell metabolism, with regard to implication in the pathogenesis of osteoporosis by IL-1β, and that TGF-β positively inhibits the bone resorption.

IgA 신병증 환자에서 신장조직내 TGF - β , IL-6 Osteopontin 및 MCP-1 유전자 발현에 관한 연구

이강욱(Kang Wook Lee),송정헌(Jung Hun Song),박기현(Ki Hyun Park),이상주(Sang Joo Lee),장윤경(Youn Kyung Chang),양종오(Jong Oh Yang),나기량(Ki Ryang Na),서광선(Kwang Sun Suh),신영태(Young Tai Shin) 대한신장학회 2001 Kidney Research and Clinical Practice Vol.20 No.4

In many experimental models and human renal diseases, TGF- 0, IL-6, osteopontin and MCP-1 have been thought to be involved in progressive re- nal injury mechanism. In order to evaluate the renal expression of these genes in six control patients (Group A) whose renal biopsy had shown only minimal lesion and no immune deposition on the light and immunofluorescent microscopic examinations and sixteen patients(Group B) who had been confirmed with primary IgA nephropathy by renal biopsy frorn Jan. 1999 to Jan. 2000 in Chungnam National University Hospital were included in this study. Competitive RT-PCR was performed to estimate the each gene studied and GAPDH expression levels of kidney biopsy specimens. The magnitude of each gene expression was represented as the ratio to GAPDH. Twenty-four hour urinary protein excretion of Group B(mean 3,882 mg/day) was significantly higher than that of Group A(mean 560 mg/day, p<0.01). The TGF- β, MCP-1, and IL-6 gene expressions of Group B(0.88±0.21, 0.85±0.14, 1.59±0.24, and 1.50±0.24, respectively) were significantly higher than those of Group B(0.19±0.14, 0.18±0.03, and 0.57±0.18, respectively, p<0.05, p<0.05, p<0.05, p<0.05). The MCP-1, osteopontin and IL-6 gene expressions of 6 IgA nephropathy patients with crescents in glomeruli and marked tubulointerstitial mononuclear cell infiltration on light microscopic examination(1.40>0.32, 2.07±0.40, 1.85>0.31, respectively) were significantly higher than those of 10 IgA nephropathy patients without crescents or marked tubulointerstitial mononuclear cell infiltration(0.59±0.24, 0.74±0.18, 1.050.18, respectively, p<0.05, p<0.05, p<0.05). The level of MCP-1 gene expression was significantly positively correlated with the magnitude of 24 hour protein excretion(r2=0.54, p<0.05). However, the level of TGF-0, osteopontin and IL-6 gene expressions were not significantly correlated with the magnitude of proteinuria. With the above results, we speculate that upregulation of osteopontin, MCP-1, IL-6 genes of the kidney may be related to rapid progressive renal in- jury process in patients with IgA nephropathy.

The Long Noncoding RNA NEAT1 Targets miR-34a-5p and Drives Nasopharyngeal Carcinoma Progression via Wnt/β-Catenin Signaling

Yuqing Ji,Man Wang,Xueshen Li,Fusheng Cui 연세대학교의과대학 2019 Yonsei medical journal Vol.60 No.4

Purpose: Long noncoding RNA nuclear paraspeckle assembly transcript 1 (NEAT1) has been deemed an oncogene in many humancancers. However, the underlying mechanism of NEAT1 in nasopharyngeal carcinoma (NPC) progression remains largelyunclear. Materials and Methods: Quantitative real-time PCR assay was performed to assess the expression of NEAT1 and miR-34a-5p inNPC tissues and cells. Western blot analysis was used to observe cell epithelial to mesenchymal transition (EMT) and the activationof Wnt/β-catenin signaling in 5-8F cells. MiRNA directly interacting with NEAT1 were verified by dual-luciferase reporter assayand RNA immunoprecipitation. Cell proliferation ability was determined by CCK-8 assay, and cell migration and invasion capacitieswere assessed by transwell assays. An animal model was used to investigate the regulatory effect of NEAT1 on tumorgrowth in vivo. Results: Our data revealed that NEAT1 is upregulated, while miR-34a-5p is downregulated in NPC tissues and cell lines. NEAT1knockdown repressed tumor growth in vitro and in vivo. Additionally, we discovered that NEAT1 directly binds to miR-34a-5pand suppresses miR-34a-5p expression. Moreover, NEAT1 knockdown exerted suppression effects on cell proliferation, migration,invasion, and EMT by miR-34a-5p. NEAT1 knockdown blocked Wnt/β-catenin signaling via miR-34a-5p. Conclusion: Our study demonstrated that NEAT1 targets miR-34a-5p at least partly to drive NPC progression by regulating Wnt/β-catenin signaling, suggesting a potential therapeutic target for NPC.

B103 세포에서 베타아밀로이드(25-35) 독성에 대한 Ginsenoside Rb_l과 Rg_l의 보호효과

이은아,주인수,허균,묵인희 대한신경과학회 1999 대한신경과학회지 Vol.17 No.5

소 β-casein 유전자 영역에서 소 Insulin-like Growth Factor 1을 생산하기 위한 Knock-in Vector

김상영,박다솜,김세은,구덕본,강만종 한국동물생명공학회(구 한국동물번식학회) 2017 Reproductive & developmental biology Vol.41 No.3

Insulin-like growth factor-1 (IGF-1) is known to play an important role in the growth of the animal. The objective of this study is construction of knock-in vector that bovine IGF-1 gene is inserted into the exon 7 locus of β-casein gene and expressed using the gene regulatory DNA sequence of bovine β-casein gene. The knock-in vector consists of 5’ arm region (1.02 kb), bIGF-1 cDNA, CMV-EGFP, and 3’ arm region (1.81 kb). To express bIGF-1 gene as transgene, the F2A sequence was fused to the 5’ terminal of bIGF-1 gene and inserted into exon 7 of the β-casein gene. As a result, the knock-in vector is confirmed that the amino acids are synthesized without termination from the β-casein exon 7 region to the bIGF-1 gene by DNA sequence. These knock-in vectors may help to create transgenic dairy cattle expressing bovine bIGF-1 protein in the mammary gland via the expression system of the bovine β-casein gene.

Substrate specificity of β-glucosidase from Gordonia terrae for ginsenosides and its application in the production of ginsenosides Rg₃, Rg₂, and Rh₁ from ginseng root extract

Shin, K.C.,Lee, H.J.,Oh, D.K. Society for Bioscience and Bioengineering, Japan ; 2015 Journal of bioscience and bioengineering Vol.119 No.5

A β-glucosidase from Gordonia terrae was cloned and expressed in Escherichia coli. The recombinant enzyme with a specific activity of 16.4 U/mg for ginsenoside Rb<SUB>1</SUB> was purified using His-trap chromatography. The purified enzyme specifically hydrolyzed the glucopyranosides at the C-20 position in protopanaxadiol (PPD)-type ginsenosides and hydrolyzed the glucopyranoside at the C-6 or C-20 position in protopanaxatriol (PPT)-type ginsenosides. The reaction conditions for the high-level production of Rg<SUB>3</SUB> from Rb<SUB>1</SUB> by the enzyme were pH 6.5, 30<SUP>o</SUP>C, 20 mg/ml enzyme, and 4 mg/ml Rb<SUB>1</SUB>. Under these conditions, G. terrae β-glucosidase completely converted Rb<SUB>1</SUB> and Re to Rg<SUB>3</SUB> and Rg<SUB>2</SUB>, respectively, after 2.5 and 8 h, respectively. Moreover, the enzyme converted Rg<SUB>1</SUB> to Rh<SUB>1</SUB> at 1 h with a molar conversion yield of 82%. The enzyme at 10 mg/ml produced 1.16 mg/ml Rg<SUB>3</SUB>, 1.47 mg/ml Rg<SUB>2</SUB>, and 1.17 mg/ml Rh<SUB>1</SUB> from Rb<SUB>1</SUB>, Re, and Rg<SUB>1</SUB>, respectively, in 10% (w/v) ginseng root extract at pH 6.5 and 30<SUP>o</SUP>C after 33 h with molar conversion yields of 100%, 100%, and 77%, respectively. The combined molar conversion yield of Rg<SUB>2</SUB>, Rg<SUB>3</SUB>, and Rh<SUB>1</SUB> from total ginsenosides in 10% (w/v) ginseng root extract was 68%. These above results suggest that this enzyme is useful for the production of ginsenosides Rg<SUB>3</SUB>, Rg<SUB>2</SUB>, and Rh<SUB>1.</SUB>