• Title/Summary/Keyword: Small protein

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Ligand-Based CoMFA Study on Pyridylpyrazolopyridine Derivatives as PKCθ Kinase Inhibitors

  • Balasubramanian, Pavithra K.;Balupuri, Anand;Cho, Seung Joo
    • Journal of Integrative Natural Science
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    • v.7 no.4
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    • pp.253-259
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    • 2014
  • Protein kinase C theta (PKC-${\theta}$) is a serine/threonine specific protein kinase. It is largely expressed in the T-cells and CD28 signaling. PKC-${\theta}$ phosphorylates diverse proteins that are involved in the various cellular signaling pathways. Activated PKC-${\theta}$ in turn activates other transcription factors that control the proliferation and differentiation of T- cells. PKC-${\theta}$ is considered to be an interesting therapeutic target due to its crucial role in the proliferation, differentiation and survival of T-cells. In the present study, we have performed ligand-based CoMFA study on a series of pyridylpyrazolopyridine derivatives as PKC-${\theta}$ inhibitors. An acceptable CoMFA model ($q^2$=0.544; ONC=4; $r^2$=0.876) was developed and validated by Bootsrapping and progressive sampling. The CoMFA contour map suggested the regions to increase the activity. Bulky substitutions in R2 position of the piperizine ring could increase the activity. Similarly positive, small substitution in the R1 position of the Pyridine ring could considerably increase the activity. Our work could assist in designing more potent PKC-${\theta}$ inhibitors of pyridylpyrazolopyridine derivatives.

Acute Phase Protein Lipocalin-2 Is Associated with Formalin-induced Nociception and Pathological Pain

  • Jha, Mithilesh Kumar;Jeon, Sangmin;Jin, Myungwon;Lee, Won-Ha;Suk, Kyoungho
    • IMMUNE NETWORK
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    • v.13 no.6
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    • pp.289-294
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    • 2013
  • Lipocalin-2 (LCN2) is an acute-phase protein induced by injury, infection, or other inflammatory stimuli. LCN2 binds small hydrophobic ligands and interacts with cell surface receptor to regulate diverse cellular processes. The role of LCN2 as a chemokine inducer in the central nervous system (CNS) has been previously reported. Based on the previous participation of LCN2 in neuroinflammation, we investigated the role of LCN2 in formalin-induced nociception and pathological pain. Formalin-induced nociceptive behaviors (licking/biting) and spinal microglial activation were significantly reduced in the second or late phase of the formalin test in Lcn2 knockout mice. Likewise, antibody-mediated neutralization of spinal LCN2 attenuated the mechanical hypersensitivity induced by peripheral nerve injury in mice. Taken together, our results suggest that LCN2 can be therapeutically targeted, presumably for both prevention and reversal of acute inflammatory pain as well as pathological pain.

Effects of Protein Contained in Major Ingredients with Treated Emulsifiers on Chemically Leavened Reduced-Calorie Cake as Baked Product Model Systems (제과제빵 모델 시스템으로서 저열량케익에 미치는 주재료 성분중 함유된 단백질 및 전처리된 유화제의 영향)

  • Kim, Hye-Young
    • Korean journal of food and cookery science
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    • v.13 no.2
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    • pp.185-191
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    • 1997
  • The effects of five hydrated emulsifiers with or without specified proteins (flour, egg) and/or polydextrose on the reduced-calorie cake as baked product model systems were compared. The small molecule amphiphiles (SMA) used were monoglycerides (MG), sorbitan monostearate (SMS), polysorbate (PS) 60, sucrose ester (SE) F7O, and SE Fl60. All flour batters with each emulsifier and supplements had similar low foam drainages (0.00∼1.03$m\ell$) indicating those systems were fairly stable in the presence of flour protein. The cake batter using starch instead of flour without egg and polydextrose and with some emulsifiers had relatively large amount of drainages (4.20∼5.87$m\ell$). When the egg and polydextrose were added to the blank cake batters using starch, foam drainages tended to show relatively low scores (0.13∼1.48$m\ell$) indicating the cake batter dispersion system is stabilized. Starch cakes made with SE F70 without egg or polydextrose(blank) unexpectedly had high volume index of 199.

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A Methylobacillus Isolate Growing Only on Methanol (메탄올만 이용하여 성장하는 Methylobacillus의 분리 및 특성)

  • 김시욱;김병홍;김영민
    • Korean Journal of Microbiology
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    • v.29 no.4
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    • pp.250-257
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    • 1991
  • An obligate methanol-oxidizing bacterium, Methylobacillus sp. strain SK1, which grows only on methanol was isolated from soil. The isolate was nonmotile Gram-negtive rod. It does not have internal membrane system. The colonies were small, whitish-yellow, and smooth. The guanine plus cytosine content of the DNA was 48 mol%. Cellular fatty acids consisted predominantly of large amounts of straight-chain saturated $C_{16:0}$ acid and unsaturated $C_{16:1}$ acid. The major ubiquinone was Q-8, and Q-10 was present as minor component. The cell was obligately aerobic and exhibited catalase, but no oxidase, activity. Poly-.betha.-hydroxybutyrate, endospores, or cysts were not observed. the isolate could grow only on methanol in mineral medium. Growth factors were not required. The isolate was unable to use methane, formaldehyde, formate, methylamine, and several other organic compounds tested as a sole source of carbon and energy. Growth was optimal at 35.deg.C and pH 7.5. It could not grow at 42.deg.C. The doubling time was 1.2h at 30.deg.C when grown with 1.0%(v/v) methanol. The growth was not affected by antibiotics inhibiting cell wall synthesis and carbon monoxide but was completely suppressed by those inhibiting protein synthesis. Methanol was found to be assimilated through the ribulose monophosphate pathway. Cytochromes of b-, c-, and o- types were found. Cell-free extracts contained a phenazine methosulfate-linked methanol dehydrogenase activity, which required ammonium ions as an activator. Cells harvested after the late exponential phase seemed to contain blue protein.ein.

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The complete chloroplast genome of Scrophularia kakudensis and a comparative analysis of S. kakudensis and S. cephalantha

  • Ogyeong SON;KyoungSu CHOI
    • Korean Journal of Plant Taxonomy
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    • v.53 no.3
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    • pp.237-241
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    • 2023
  • The genus Scrophularia L. (Scrophulariaceae) comprises 200-270 species worldwide and is a taxonomically challenging lineage, displaying morphological diversity and hybridization. S. kakudensis is morphologically similar to the closely related taxa S. kakudensis var. microphylla, S. pilosa, and S. cephalantha. Therefore, the purpose of this study was to sequence the chloroplast (cp) genome of S. kakudensis using next-generation sequencing and compare it to those of related taxa. The complete cp genome sequence of Scrophularia kakudensis was found to be 152,355 bp long, consisting of a pair of inverted repeats of 25,485 bp that separate a large single-copy (LSC) of 83,479 bp from small single-copy regions of 17,909 bp. The cp genome contained 78 protein-coding genes, 30 tRNAs, and four rRNAs. A phylogenetic analysis based on 78 protein-coding genes from six Scrophularia species showed S. kakudensis and S. cephalantha formed with 100% bootstrap values. We compared the complete cp genomes of S. kakudensis and S. cephalantha and identified seven sequence divergence regions: matK/rps16, rps16/trnQ, trnS/trnG, rpoB/trnC, trnS/trnG, rpl32/trnL, and ndhD/psaC. These regions may be useful for determining the phylogenetic relationships among S. kakudensis-related species.

FAP Inhibitors as Novel Small Molecules for Cancer Imaging using Radionuclide

  • Anvar Mirzaei;Jung-Joon Min;Dong-Yeon Kim
    • Journal of Radiopharmaceuticals and Molecular Probes
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    • v.9 no.1
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    • pp.49-55
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    • 2023
  • Tumors are encircled by various non-cancerous cell types in the extracellular matrix, including fibroblasts, endothelial cells, immune cells, and cytokines. Fibroblasts are the most critical cells in the tumor stroma and play an important role in tumor development, which has been highlighted in some epithelial cancers. Many studies have shown a tight connection between cancerous cells and fibroblasts in the last decade. Regulatory factors secreted into the tumor environment by special fibroblast cells, cancer-associated fibroblasts (CAFs), play an important role in tumor and vessel development, metastasis, and therapy resistance. This review addresses the development of FAP inhibitors, emphasizing the first, second, and latest generations. First-generation inhibitors exhibit low selectivity and chemical stability, encouraging researchers to develop new scaffolds based on preclinical and clinical data. Second-generation enzymes such as UAMC-1110 demonstrated enhanced FAP binding and better selectivity. Targeted treatment and diagnostic imaging have become possible by further developing radionuclide-labeled fibroblast activation protein inhibitors (FAPIs). Although all three FAPIs (01, 02, and 04) showed excellent preclinical and clinical findings. The final optimization of these FAPI scaffolds resulted in FAPI-46 with the highest tumor-to-background ratio and better binding affinity.

Roles of RasU in Cell Motility and Development

  • Uri Han;Taeck Joong Jeon
    • Journal of Integrative Natural Science
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    • v.16 no.2
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    • pp.47-51
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    • 2023
  • Ras small GTPases are involved in regulating various cellular signaling pathways including cell migration, proliferation, and differentiation. Ras GTPase subfamily is comprised of 15 proteins; 11 Ras, 3 Rap, and one Rheb related protein. Some Ras proteins, such as RasC and RasG, have been identified for their major functions, but there are proteins whose functions have not been studied yet, such as RasU and RasX. Here, we investigated the roles of RasU in cell motility and development. RasU shows the highest homology with RasX. To investigate the functions of RasU, rasU null cells were used to observe the phenotype. Cells lacking RasU were larger and more spread than wild-type cells. These results indicate that RasU plays a negative role in cell spreading. In addition, we investigated the roles of RasU in cell motility and development of Dictyostelium cells and found that rasU null cells exhibited decreased random migration speed and delayed developmental process. These results suggest that RasU plays an important role in cell motility and development.

Lichen as Bioindicators: Assessing their Response to Heavy Metal Pollution in Their Native Ecosystem

  • Jiho Yang;Soon-Ok Oh;Jae-Seoun Hur
    • Mycobiology
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    • v.51 no.5
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    • pp.343-353
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    • 2023
  • Lichens play crucial roles in the ecosystems, contributing to soil formation and nutrient cycling, and being used in biomonitoring efforts to assess the sustainability of ecosystems including air quality. Previous studies on heavy metal accumulation in lichens have mostly relied on manipulated environments, such as transplanted lichens, leaving us with a dearth of research on how lichens physiologically respond to heavy metal exposure in their natural habitats. To fill this knowledge gap, we investigated lichens from two of South Korea's geographically distant regions, Gangwon Province and Jeju Island, and examined whether difference in ambient heavy metal concentrations could be detected through physiological variables, including chlorophyll damage, lipid oxidation, and protein content. The physiological variables of lichens in response to heavy metals differed according to the collection area: Arsenic exerted a significant impact on chlorophyll degradation and protein content. The degree of fatty acid oxidation in lichens was associated with increased Cu concentrations. Our research highlights the value of lichens as a bioindicator, as we found that even small variations in ambient heavy metal concentrations can be detected in natural lichens. Furthermore, our study sheds light on which physiology variables that can be used as indicators of specific heavy metals, underscoring the potential of lichens for future ecology studies.

Inhibition of protein kinase CK2 facilitates cellular senescence by inhibiting the expression of HO-1 in articular chondrocytes

  • Kang Mi Kim;Dong Hyun Sohn;Koanhoi Kim;Young Chul Park
    • International Journal of Molecular Medicine
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    • v.43 no.2
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    • pp.1033-1040
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    • 2019
  • Protein kinase casein kinase 2 (CK2) is important in the regulation of cell proliferation and death, even under pathological conditions. Previously, we reported that CK2 regulates the expression of heme oxygenase-1 (HO-1) in stress-induced chondrocytes. In the present study, it was shown that CK2 is involved in the dedifferentiation and cellular senescence of chondrocytes. Treatment of primary articular chondrocytes with CK2 inhibitors, 4,5,6,7-terabromo-2-azabenzimidazole (TBB) or 5,6-dichlorobenzimidazole 1-β-D-ribofuranoside (DRB), induced an increase in senescence-associated β-galactosidase (SA-β-gal) staining. In addition, TBB reduced the expression of type II collagen and stimulated the accumulation of β-catenin, phenotypic markers of chondrocyte differentiation and dedifferentiation, respectively. It was also observed that the abrogation of CK2 activity by CK2 small interfering RNA induced phenotypes of chondrocyte senescence. The association between HO-1 and cellular senescence was also examined in CK2 inhibitor-treated chondrocytes. Pretreatment with 3-morpholinosydnonimine hydrochloride, an inducer of the HO-1 expression, or overexpression of the HO-1 gene significantly delayed chondrocyte senescence. These results show that CK2 is associated with chondrocyte differentiation and cellular senescence and that this is due to regulation of the expression of HO-1. Furthermore, the findings suggest that CK2 is crucial as an anti-aging factor during chondrocyte senescence.

The Comparison of Protein Patterns of Sera in Non-Pregnant and Pregnant Women (非姙娠 및 姙娠한 女子의 血淸蛋白質 패턴의 比較)

  • Ha, Man-Joon;Park, Won-Chul
    • The Korean Journal of Zoology
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    • v.29 no.2
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    • pp.86-106
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    • 1986
  • For the comparative study of protein patterns of the sera of pregnant women, the protein in sera of normal male subjects, non-pregnant women, pregnant women and women delivered of children were analyzed by using the methods of SDS/polyacrylamide gel electrophoresis, two-dimensional electrophoresis and amino acid analysis. The results were as follows: 1. When the protein patterns of sera in normal male ranging from 10, 000 to 110, 000 daltons were compared to non-pregnant women by SDS/polyacrylamide gel electrohporesis, their protein patterns were same each other numerically but bands 3(22, 000 dalton) and 6(39, 000) were less in male than in non-pregnant women quantitatively. When the protein patterns in the pregnant women in which serum were collected two week intervals were compared with non-pregnant women, there was increased or decreased in several bands quantitavely. The protein patterns of sera in pregnant women were compared with those of non-pregnant women; band 3(22, 000) showed similar patterns each other until the 16th week but the quantity of protein was decreased continously from the 18th week to the third trimester of pregnancy. Contary, bands 4(24, 000), 9(69, 000), 10(70, 000), 12(80, 000), 14(86, 000), 15(91, 000) and 16(94, 000) were gradually increased in quantity from the begining of gestation, and band 7(51, 000) was increased until the 32th week of gestation only but somewhat decreased after this time. The quantities of bands 12(80, 000), 15(91, 000) and 16(94, 000) were relatively increased when the protein patterns of delivered women were compared with those of the third trimester of pregnancy. Women who were dilivered female children showed more increase in bands 4(24, 000), 7(51, 000) and 10(70, 000)than one who were delivered male chilren. 2. When the protein patterns of sera in normal males were compared with those of nonpregnant women by two-dimensional electrophoresis, three spots of spot a group were not appeared in the males and the spot c group in the males was less than in the non-pregnant women. In the pregnant women, albumin was significantly decreased during the 10-12 week of gestation but recovered after these times. And spot f(70, 000) was decreased in the 10th week of gestation but increased from this time. 3. Glutamic acid, lysine, aspartic acid, leucine and valine in pregnant women were large in quantity while methionine, isoleucine and glycine were small in quantity by amino acid analysis. The total amino acids were increased remarkably in the second trimester of pregnancy but began to decrease in the third trimester of pregnancy. As mentioned, this present paper deat with that proteins which consist of maternal serum were increased with specific period in pregnancy and that the change of characteristic protein patterns were identified in the serum protein of each trimester in the pregnant women. And furthermore, the study should be preformed for the sex-identification of a fetus in the early pregnancy.

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