• 제목/요약/키워드: physiological inhibitors

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Role of Calcium in the Osmoregulation under Salt Stress in Dunaliella salina

  • Lee, Sun-Hi
    • Journal of Plant Biology
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    • 제38권3호
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    • pp.243-250
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    • 1995
  • Involvement of calcium in signal transduction of salt stress was investigated in 1.7 M NaCl adapted Dunaliella salina, extremely halotolerant, unicellular green alga. When hyperosmotic (3.4 M NaCl) or Hypoosmotic (0.8 M NaCl) stress was treated, extracellular calcium was influxed in or intracellular calcium effluxed from D. salina, respectively, and these fluxes were proportional to the degree of stress. This might indicate indirectly that the change of calcium level occurred within the cells. In addition, the change of calcium flux was ahead of glycerol synthesis which has been known as the physiological response to salt stress. Osmoregulation was affected byextracellular calcium concentration, and increase of glycerol content as an osmoticum was inhibited about 50% by treatment of TFP and W-7 known as calmodulin specific inhibitors. Furthermore, in the case of the hyperosmotic stressed cells, the amount of 21 kD and 39 kD protein appeared to be calcium binding protein were increased. Among these, the 39 kD protein was detected only in the hyperosmotic stressed cells. The results obtained in the present work suggest that the possibility of calcium as a second messenger in the transduction of salt stress signal exists in the osmoregulation system of D. salina.

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매괴화(玫瑰花) 추출물의 아세틸콜린에스테라제, 베타 시크리타제 및 베타 아밀로이드 응집에 대한 저해효과 (Inhibitory Effects of Extract of Rosae Rugosae Flos on the Acetylcholinesterase, β-secretase, and β-amyloid Aggregation)

  • 김효신;김주은;임재윤
    • 동의생리병리학회지
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    • 제30권1호
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    • pp.33-39
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    • 2016
  • Alzheimer's disease(AD), one of the most common forms of dementia, is characterized pathologically by the presence of intracellular neurofibrillary tangles and deposition of β-amyloid(Aβ) peptides of 40-42 residues. Aβ has been believed to be neurotoxic and now is also considered to have a role on the mechanism of memory dysfunction. Only a few acetylcholinesterase(AChE) inhibitors have been developed for treatment of AD, although the numbers of patients are rapidly increasing within aging society. Here, we show that ethanol extract of Rosae Rugosae Flos(RR) or its butanol fraction reduce the enzyme activity of AChE and BACE1(β-site APP cleaving enzyme 1). Furthermore, We found that RR inhibits Aβ aggregation and removes Aβ aggregates by Transmission electron microscopy(TEM). In addition, RR reduces the free radical of 2, 2-diphenyl-1-picrylhydrazyl(DPPH). We suggest that Rosae Rugosae Flos may be useful as a herbal medicine to treat AD.

천궁 메탄올 추출액의 멜라닌 형성 억제 효과 (Inhibitory Effect of Methanolic Extract of Cnidii Rhizoma on the Melanogenesis)

  • 박종훈;김양진;문연자;이영철;우원홍
    • 동의생리병리학회지
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    • 제19권4호
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    • pp.938-944
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    • 2005
  • Down-regulation of melanin synthesis is required for recovery of pigmentary disorders and it is known that direct inhibitors of tyrosinase suppress melanin synthesis. We screened several oriental medicinal plants using B16/Fl0 cells and found that the methanolic extract of Cnidii Rhizoma down-regulated melanin synthesis effectively. Although the proliferation of Bl6/Fl0 cells was decresed by the methanolic extract of Cnidii Rhizoma, it did not appear necrosis. Bl6/F10 cells incubated with the methanolic extract of Cnidii Rhizoma showed reduced pigmentation and tyrosinase activity. Western blotting revealed that the amount of tyrosinase was decreased by the methanolic extract of Cnidii Rhizoma. These results suggest that the inhibitary effect of the methanolic extract of Cnidii Rhizoma on melanogenesis is due to the suppression of tyrosinase in Bl6/F10 cells and Cnidii Rhizoma is a candidate for an efficient whitening agent.

Signaling Molecules at the Conceptus-Uterine Interface during Early Pregnancy in Pigs

  • Seo, Heewon;Choi, Yohan;Shim, Jangsoo;Kim, Mingoo;Ka, Hakhyun
    • 한국수정란이식학회지
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    • 제27권4호
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    • pp.211-221
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    • 2012
  • The process of embryo implantation requires physical contact and physiological communication between the conceptus trophectoderm and the maternal uterine endometrium. During the peri-implantation period in pigs, the conceptus undergoes significant morphological changes and secretes estrogens, the signal for maternal recognition of pregnancy. Estrogens secreted from the conceptus act on uterine epithelia to redirect $PGF_2{\alpha}$, luteolysin, secretion from the uterine vasculature to the uterine lumen to prevent luteolysis as well as to induce expression of endometrial genes that support implantation and conceptus development. In addition, conceptuses secrete cytokines, interferons, growth factors, and proteases, and in response to these signals, the uterine endometrium produces hormones, protease inhibitors, growth factors, transport proteins, adhesion molecules, lipid molecules, and calcium regulatory molecules. Coordinated interactions of these factors derived from the conceptus and the uterus play important roles in the process of implantation in pigs. To better understand mechanism of implantation process in pigs, this review provides information on signaling molecules at the conceptus-uterine interface during early pregnancy, including recently reported data reported.

Development of a High Efficient "Dual Bt-Plus" Insecticide Using a Primary Form of an Entomopathogenic Bacterium, Xenorhabdus nematophila

  • Eom, Seonghyeon;Park, Youngjin;Kim, Hyeonghwan;Kim, Yonggyun
    • Journal of Microbiology and Biotechnology
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    • 제24권4호
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    • pp.507-521
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    • 2014
  • A phase variation has been reported in an entomopathogenic bacterium, Xenorhabdus nematophila. Compared with a wild-type primary form, a secondary form usually loses several physiological and biochemical characters. This study showed that the phase variation of X. nematophila caused a significant alteration in its immunosuppressive activity and subsequent entomopathogenicity. A secondary form of X. nematophila was detected in laboratory colonies and exhibited significant differences in dye absorption and entomopathogenicity. In addition, the secondary form was different in its production of eicosanoid-biosynthesis inhibitors (EBIs) compared with the primary form of X. nematophila. Production of oxindole and p-hydroxypropionic acid was significantly reduced in the culture broth of the secondary form of X. nematophila. The reduced EBI production resulted in significant suppression in the inhibitory effects on cellular nodule formation and phenoloxidase activity. Culture broth of the primary form of X. nematophila enhanced the pathogenicity of Bacillus thuringiensis ( Bt) significantly more than the culture broth of the secondary form. Furthermore, this study developed a highly efficient "Dual Bt-Plus: to control both lepidopteran insect pests Plutella xylostella and Spodoptera exigua, by mixing two effective Bt strains along with the addition of potent bacterial metabolites or 100-fold concentrated X. nematophila culture broth.

P56 LCK Inhibitor Identification by Pharmacophore Modelling and Molecular Docking

  • Bharatham, Nagakumar;Bharatham, Kavitha;Lee, Keun-Woo
    • Bulletin of the Korean Chemical Society
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    • 제28권2호
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    • pp.200-206
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    • 2007
  • Pharmacophore models for lymphocyte-specific protein tyrosine kinase (P56 LCK) were developed using CATALYST HypoGen with a training set comprising of 25 different P56 LCK inhibitors. The best quantitative pharmacophore hypothesis comprises of one hydrogen bond acceptor, one hydrogen bond donor, one hydrophobic aliphatic and one ring aromatic features with correlation coefficient of 0.941, root mean square deviation (RMSD) of 0.933 and cost difference (null cost-total cost) of 66.23. The pharmacophore model was validated by two methods and the validated model was further used to search databases for new compounds with good estimated LCK inhibitory activity. These compounds were evaluated for their binding properties at the active site by molecular docking studies using GOLD software. The compounds with good estimated activity and docking scores were evaluated for physiological properties based on Lipinski's rules. Finally 68 compounds satisfied all the properties required to be a successful inhibitor candidate.

Sensitization of Vanilloid Receptor Involves an Increase in the Phosphorylated Form of the Channel

  • Lee Soon-Youl;Lee Jae-Hag;Kang Kwon Kyoo;Hwang Sue-Yun;Choi Kang Duk;Oh Uhtaek
    • Archives of Pharmacal Research
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    • 제28권4호
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    • pp.405-412
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    • 2005
  • A vanilloid receptor (VR1, now known as TRPV1) is an ion channel activated by vanilloids, including capsaicin (CAP) and resiniferatoxin (RTX), which are pungent ingredients of plants. Putative endogenous activators (anandamide and metabolites of arachidonic acid) are weak activators of VR1 compared to capsaicin and RTX, and the concentrations of the physiological condition of those activators are not sufficient to induce significant activation of VR1. One way to overcome the weak activation of endogenous activators would be the sensitization of VR1, with the phosphorylation of the channel being one possibility. The phosphorylation of VR1 by several kinases has been reported, mostly by indirect evidence. Here, using an in vivo phosphorylation method, the VR1 channel was shown to be sensitized by phosphorylation of the channel itself by multiple pathways involving PKA, PKC and acid. Also, in sensitizing VR1, BK appeared to show activation of PKC for the sensitization of VR1 by phosphorylation of the channel.

Inhibitory Effect of Genistein on Agonist-Induced Modulation of Vascular Contractility

  • Je, Hyun Dong;Sohn, Uy Dong
    • Molecules and Cells
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    • 제27권2호
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    • pp.191-198
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    • 2009
  • The present study was undertaken to determine whether treatment with genistein, the plant-derived estrogen-like compound influences agonist-induced vascular smooth muscle contraction and, if so, to investigate related mechanisms. The measurement of isometric contractions using a computerized data acquisition system was combined with molecular experiments. Genistein completely inhibited KCl-, phorbol ester-, phenylephrine-, fluoride- and thromboxane $A_2$-induced contractions. An inactive analogue, daidzein, completely inhibited only fluoride-induced contraction regardless of endothelial function, suggesting some difference between the mechanisms of RhoA/Rho-kinase activators such as fluoride and thromboxane $A_2$. Furthermore, genistein and daidzein each significantly decreased phosphorylation of MYPT1 at Thr855 had been induced by a thromboxane $A_2$ mimetic. Interestingly, iberiotoxin, a blocker of large-conductance calcium-activated potassium channels, did not inhibit the relaxation response to genistein or daidzein in denuded aortic rings precontracted with fluoride. In conclusion, genistein or daidzein elicit similar relaxing responses in fluoride-induced contractions, regardless of tyrosine kinase inhibition or endothelial function, and the relaxation caused by genistein or daidzein was not antagonized by large conductance $K_{Ca}$-channel inhibitors in the denuded muscle. This suggests that the RhoA/Rho-kinase pathway rather than $K^+$- channels are involved in the genistein-induced vasodilation. In addition, based on molecular and physiological results, only one vasoconstrictor fluoride seems to be a full RhoA/Rho-kinase activator; the others are partial activators.

Shikonin Modulates Cell Proliferation by Inducing Apoptosis in LLC Cells via MAPK Regulation and Caspase Activation

  • 이수진;김성훈
    • 동의생리병리학회지
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    • 제19권2호
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    • pp.501-507
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    • 2005
  • Shikonin is a chemically characterized component of traditional herbal medicine, the root of Lithospermum erythrorhizon and has been shown to possess antitumor activities. Here we investigated anticancer potential of shikonin and its possible mechanism of action in LLC cells. Shikonin inhibited the proliferation of LLC cells in a concentration-dependent manner. It was also demonstrated that shikonin induced apoptosis in LLC cells by Annexin V staining and TUNEL staining analysis. Shikonin treatment was caused that decrease of Bcl-2, activation of caspases and cleavage of PARP. And shikonin also induced that the activation of mitogen-activated protein kinases (MAPKs), such as extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and p38. Interestingly, the cell proliferation inhibition induced by shikonin was recovered by specific inhibitors of JNK and p38 but the inhibitor of MEK, the upstream kinase of ERK, did not recover. Additionally, shikonin administration at doses of 5 mg/kg in C57BL/6 mice strongly inhibited the primary tumor growth of LLC. Taken together, these results suggest that shikonin may suppress LLC cell proliferation by inducing an apoptotic process via activation of caspases and MAPKs

Alleviation of imiquimod-induced psoriasis-like symptoms in Rorα-deficient mouse skin

  • Koog Chan Park;Jiwon Kim;Aram Lee;Jong-Seok Lim;Keun Il Kim
    • BMB Reports
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    • 제56권5호
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    • pp.296-301
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    • 2023
  • Retinoic acid receptor-related orphan receptor α (RORα) plays a vital role in various physiological processes, including metabolism, cancer, circadian rhythm, cerebellar development, and inflammation. Although RORα is expressed in the skin, its role in skin physiology remains poorly elucidated. Herein, Rorα was expressed in the basal and suprabasal layers of the epidermis; however, keratinocyte-specific Rorα deletion did not impact normal epidermal formation. Under pathophysiological conditions, Rorα-deficient mice exhibited alleviated psoriasis-like symptoms, including relatively intact epidermal stratification, reduced keratinocyte hyperproliferation, and low-level expression of inflammatory cytokines in keratinocytes. Unexpectedly, the splenic population of Th17 cells was significantly lower in keratinocyte-specific RORα deficient mice than in the control. Additionally, Rorα-deficiency reduced imiquimod-induced activation of nuclear factor-κB and STAT3 in keratinocytes. Therefore, we expect that RORα inhibitors act on immune cells and keratinocytes to suppress the onset and progression of psoriasis.