• 대한약침학회지
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• 제22권4호
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• pp.248-252
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• 2019

Objectives: The aim of the present work is evaluating the special effects of Urtica Dioica and Lamium Album on the serum level of K-Ras and GSK-3 beta in diabetic rats. Methods: In the present experimental study, 32 male Wistar rats randomly divided into 4 groups (Group I: normal control rats; receiving daily PBS, Group 2: diabetic control rats; receiving single dose of streptozotocin (60 mg/kg) and daily PBS, Group 3: Diabetic rats treated with 100 mg/kg of hydroalcoholic extract of the U. dioica, Group 4: Diabetic rats treated with 100 mg/kg of hydroalcoholic extract of L. Album. Diabetes-induced by an intraperitoneal injection of streptozotocin (60 mg/ kg). On the 14 th day of treatment, the weight, fasting blood sugar (FBS) and on 28 th day blood glucose, K-Ras and GSK3 beta was measured. Results: In diabetic group blood GSK- 3 beta increase in comparison to control group (P < 0.05), also blood K-Ras decrease in the diabetic group (P < 0.05). Both extracts reduced GSK-3 beta level, however, this reduction was only statistically significant by U.dioica (P < 0.05). Compared to diabetic group, blood K-Ras level increased by both extract (P < 0.05). Also diabetes induction increase blood glucose levels and both extracts decrease its level significantly (P < 0.05).there is no significant differences among both extract effects on blood glucose, and K-Ras. Conclusion: For the first time shown that both extracts by regulating GSK-3 beta and K-Ras improve blood glucose level. More studies are needed to determine all the effects of these herbs.

• 생물정신의학
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• 제6권1호
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• pp.67-73
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• 1999

The cAMP-dependent protein kinase(PKA) is an intracellular enzyme with serine-threonine kinase activity that plays a key role in cell growth, differentiation, and apoptosis in eukaryotes. In order to understand the PKA signal transduction pathway regulating cell life cycle and identify its role, we focused on the characterization of up-/down-regulated genes by PKA using the differential display polymerase chain reaction. Seven differentially expressed sequence tags(DEST) have been obtained. Among these DESTs, 2 DESTs were homologous to the sequence of genes from BLAST search result. KC1-5 DEST that was up-regulated in A123.7 cells was highly corresponded to mouse apoptosis-related gene(MA-3) or mouse mRNA for topoisomerase inhibitor suppressed(TIS). MA-3 was induced in various types of apoptosis, specially in NGF-deprived apoptotic PC12 cells. TIS was down-regulated in the RVC lymphoma cells incubated with topoisomerase inhibitor that induces DNA strand breakages. PG1-1 DEST that was highly expressed in PC12 cells was corresponded to transposon Tn10 3'-end. Tnansposon Tn10 was up-regulated in differentiated myeloblastic ML-1 cells by 12-O-tetradecanoylphorbol-13-acetate. This study illuminates that MA-3/TIS was down-regulated by PKA activity, and transposon Tn10 was up-regulated by it.

• 생약학회지
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• 제45권4호
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• pp.288-293
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• 2014

The present study was conducted to evaluate the hair growth-promoting effect of Clitocybin A from mushroom Clitocybe aurantiaca with dermal papilla cells (DPCs), which play important roles in the regulation of hair cycle. Clitocybin A significantly increased the proliferation of immortalized rat vibrissa DPCs. Flow cytometry analysis revealed that Clitocybin A promoted cell-cycle progression through G0/G1 to S phase in immortalized rat vibrissa DPCs. In addition, Clitocybin A increased the level of cell cycle proteins such as cyclin D1, phospho-pRB, and phospho-CDK2. To elucidate the molecular mechanisms of Clitocybin A on the proliferation of DPCs, we examined the activation of wnt/${\beta}$-catenin signaling which is known to regulate hair follicle development, differentiation and hair growth. Clitocybin A activated wnt/${\beta}$-catenin signaling via the increase of phospho(ser552)-${\beta}$-catenin, phospho(ser675)-${\beta}$-catenin and phospho(ser9)-$GSK3{\beta}$. Furthermore, Clitocybin A markedly increased the activation of extracellular signal-regulated kinase (ERK). These results suggest that the Clitocybin A may induce hair growth by proliferation of DPCs via cell-cycle progression as well as the activation of Wnt/${\beta}$-catenin signaling and ERK pathway.

• The Plant Pathology Journal
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• 제23권2호
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• pp.76-89
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• 2007

CaCDPK4, a full-length cDNA clone encoding Capsicum annuum calcium-dependent protein kinase 4, was isolated from chili pepper (Capsicum annuum L.). Deduced amino acid sequence of CaCDPK4 shares the highest homology with tobacco NpCDPK8 and chickpea CaCDPK2 with 79% identity. Genomic blot analyses revealed that CaCDPK4 is present as a single copy in pepper genome, but it belongs to a multigene family. CaCDPK4 was highly induced when pepper plants were inoculated with an incompatible bacterial pathogen. Induced levels of CaCDPK4 transcripts were also detected in pepper leaves by the treatment of ethephon, an ethylene-inducing agent, and high-salt stress condition. The bacterial-expressed GST-CaCDPK4 protein showed to retain the autophosphorylation activity in vitro. GUS expression driven by CaCDPK4 promoter was examined in transgenic Arabidopsis containing transcriptional fusion of CaCDPK4 promoter. GUS expression under CaCDPK4 promoter was strong in the root and veins of the seedlings. GW (-1965) and D3 (-1377) promoters conferred on GUS expression in response to inoculation of an incompatible bacterial pathogen, but D4-GUS (-913) and DS-GUS (-833) did not. Taken together, our results suggest that CaCDPK4 can be implicated on signal transduction pathway of defense response against an incompatible bacterial pathogen in pepper.

• Molecular & Cellular Toxicology
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• 제4권1호
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• pp.78-84
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• 2008

EGFR has been intensively investigated as a target to block the signal transduction pathway which stimulates cancer growth and metastasis. Studies about structure-activity relationship for tricyclic azepine derivatives were performed with topomer-CoMFA. The derived topomer-CoMFA model with steric and electrostatic field parameters based on fragment units gave reasonable statistics ($q^2$=0.561, $r^2$=0.679). The model explains why a halogen atom at the meta position of aniline is important to increases inhibitory activity. This comes from an electrostatically negative groups are favored near this region. The model also shows that there are sterically favored regions around methoxy group extended from oxazepine derivatives. The findings about steric and electrostatic effects can be utilized for designing new inhibitors.

• 미생물학회지
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• 제47권2호
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• pp.167-169
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• 2011

Saccharomyces cerevisiae ${\Sigma}1278b$ 균주는 FLO8 유전자를 가지고 있는 반면, S288c 균주는 flo8 정지돌연변이를 포함하고 있어서 반수체의 부착 생장, 배수체의 위균사형 생장 및 생물막 형성 현상을 보이지 않는다. S. cerevisiae의 LAMMER kinase인 ScKns1의 기능을 파악하기 위한 온도 감수성 실험을 수행한 결과, S288c 균주와 달리 ${\Sigma}1278b$ 균주가 $37^{\circ}C$의 열 스트레스에 민감함을 발견하였으며, 흥미롭게도 $Sckns1{\Delta}$ 돌연변이가 이러한 감수성을 회복시킴을 확인하였다. 또한 ${\Sigma}1278b$ 균주의 열 감수성은 삼투안정제인 sorbitol의 첨가에 의해 회복되었다. 이러한 결과는 Flo8은 ScKns1이 연관된 열 스트레스를 조절하는 신호전달경로를 구성할 가능성을 제시한다.

• 한국균학회지
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• 제39권1호
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• pp.85-87
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• 2011

C. albicans는 사람에게 병증을 유발하는 기회감염성 진균으로 효모형에서 균사형 및 위균사형으로 전환할 수 있다. 이러한 이형성의 감소나 상실은 병원성의 결여와 연관되어 있기에 C. albicans의 병원성에 가장 결정적인 요인으로 여겨진다. 선행 실험을 통하여 이중특이성 인산화 효소의 결손 균주에서 이형성의 감소를 관찰하였기에, 마우스 모델에서 병원성에 미치는 효과를 확인하고자 하였다. 이중특이성 인산화 효소의 결손 균주를 감염시킨 경우, 마우스의 생존기간이 약 15일로 야생형의 3.9일보다 증가하였다. 또한 신장조직에 침투한 C. albicans의 세포수는 야생형에 비해 10배 가량 감소하였다. 본 연구는 C. albicans에서 이형성과 병원성에 연관된 이중특이성 인산화효소에 의한 새로운 신호전달기작의 가능성을 제시한다.

• BMB Reports
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• 제36권3호
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• pp.326-331
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• 2003

The fission yeast cells that contained the cloned glutathione synthetase (GS) gene showed 1.4-fold higher glutathione (GSB) content and 1.9-fold higher GS activity than the cells without the cloned GS gene. Interestingly, $\gamma$-glutamylcysteine synthetase activity increased 2.1-fold in the S. pombe cells that contained the cloned GS gene. The S. pombe cells that harbored the multi copy-number plasmid pRGS49 (containing the cloned GS gene) showed a higher level of survival on solid media with cadmium chloride (1 mM) or mercuric chloride ($10\;{\mu}M$) than the cells that harbored the YEp357R vector. The 506 bp upstream sequence from the translational initiation point and N-terminal8 amino acid-coding region were fused into the promoteriess $\beta$-galactosidase gene of the shuttle vector YEp367R to generate the fusion plasmid pUGS39. Synthesis of $\beta$-galactosidase from the fusion plasmid pUGS39 was significantly enhanced by cadmium chloride and NO-generating S-nitroso-N-acetylpenicillamine (SNAP) and sodium nitroprusside (SN). It was also induced by L-buthionine-(S,R)-sulfoximine, a specific inhibitor of $\gamma$-glutamylcysteine synthetase (GCS). We also found that the expression of the S. pombe GS gene is regulated by the Atf1-Spc1-Wis1 signal pathway.

• 한국한의학연구원논문집
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• 제13권2호통권20호
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• pp.157-164
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• 2007

An imbalance in bone remodeling that is caused by increased bone resorption over bone formation leads to most adult skeletal diseases including osteoporosis. Since the development of anti-resorptive agents from natural substances has recently gained more interest in the treatment of osteoporosis, we evaluated the effects of 222 natural compounds on receptor activator of $NF-{\kappa}B$ ligand (RANKL)-induced of tartrate-resistance acid phosphatase (TRAP) activity in RAW264.7 murine macrophage cell, and found that berberine chloride is one of compounds inhibiting RANKL-induced TRAP activity. Berberine chloride significantly inhibited the RANKL-induced TRAP activity and the formation of multinucleated osteoclasts in a dose-dependent manner. In addition, berberine chloride prevented the RANKL-induced mRNA expression of TRAP, matrix metalloproteinase 9 and c-Src, which have been known to be highly expressed in the process of osteoclastogenesis. Interestingly, berberine chloride prevented the RANKL-induced activation of extracellular signal-regulated kinase (ERK) which is one of mitogen-activated protein (MAP) kinases. In conclusion, berberine chloride could inhibit the osteoclastogenesis via preventing the activation of ERK/MAP kinase signaling pathway.

• 대한한의학방제학회지
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• 제21권2호
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• pp.53-62
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• 2013

Objectives : Diabetic nephropathy is associated with morbidity and mortality of diabetes mellitus patients. Mesangial cell proliferation is known as the major pathologic features such as glomerulosclerosis. Oryeong-san, Korean formula, is widely used for the treatment of nephrosis, edema, and uremia. Oryeong-san is composed of five herbs: Alismatis Rhizoma, Polyporus, Atractylodis Rhizoma Alba, Hoelen, and Cinnamomi Cortex. Methods : The present study was performed to investigate potent inhibitory effect of Oryeong-san on high glucose (HG)-induced rat mesangial cells (RMC) proliferation. Results : RMC proliferation under 25 mM glucose was significantly accelerated compared with 5.5 mM glucose, which was inhibited by Oryeong-san in dose dependent manner. Pre-treatment of Oryeong-san induced down-regulation of cyclins/CDKs and up-regulation of CDK inhibitor, p21waf1/cip1 and p27kip1 expression. In addition, Oryeong-san reduced HG-induced RMC proliferation by suppressed the mitogen-activated protein kinase (MAPK) phospholyration such as extracellular signal regulated kinase (ERK), Jun N-terminal Kinase (JNK), and p38. Oryeong-san significantly suppressed HG-induced ROS production. Conclusions : Oryeong-san consequently inhibited HG-induced mesangial cell proliferation through the inhibition of MAPK and ROS signaling pathway. These results suggest that Oryeong-san may be effective in the treatment of renal dysfunction leading to diabetic nephropathy.