• 제목/요약/키워드: Receptor model

검색결과 858건 처리시간 0.037초

Schisandrin A in Schisandra chinensis Upregulates the LDL Receptor by Inhibiting PCSK9 Protein Stabilization in Steatotic Model

  • Hyo-Jin Kim;Seon Kyeong Park;Soo Hyun Park;Yu Geon Lee;Jae-Ho Park;Jin-Taek Hwang;Min-Yu Chung
    • Journal of Microbiology and Biotechnology
    • /
    • 제34권2호
    • /
    • pp.425-435
    • /
    • 2024
  • Schisandra chinensis extract (SCE) protects against hypocholesterolemia by inhibiting proprotein convertase subtilisin/kexin 9 (PCSK9) protein stabilization. We hypothesized that the hypocholesterolemic activity of SCE can be attributable to upregulation of the PCSK9 inhibition-associated low-density lipoprotein receptor (LDLR). Male mice were fed a low-fat diet or a Western diet (WD) containing SCE at 1% for 12 weeks. WD increased final body weight and blood LDL cholesterol levels as well as alanine transaminase and aspartate aminotransferase expression. However, SCE supplementation significantly attenuated the increase in blood markers caused by WD. SCE also attenuated WD-mediated increases in hepatic LDLR protein expression in the obese mice. In addition, SCE increased LDLR protein expression and attenuated cellular PCSK9 levels in HepG2 cells supplemented with delipidated serum (DLPS). Non-toxic concentrations of schisandrin A (SA), one of the active components of SCE, significantly increased LDLR expression and tended to decrease PCSK9 protein levels in DLPS-treated HepG2 cells. High levels of SA-mediated PCSK9 attenuation was not attributable to reduced PCSK9 gene expression, but was associated with free PCSK9 protein degradation in this cell model. Our findings show that PCSK9 secretion can be significantly reduced by SA treatment, contributing to reductions in free cholesterol levels.

Interactions of Peptides with Model Membrane Systems Studied by NMR Spectroscopy

  • Kim, Yangmee
    • 한국생물물리학회:학술대회논문집
    • /
    • 한국생물물리학회 1999년도 학술발표회 진행표 및 논문초록
    • /
    • pp.19-19
    • /
    • 1999
  • The functions and the medicinal values of peptides are closely related to their structures. Most of the peptides function in the mediation of the membrane. Biological membrane serves important functions in the binding of peptide to a membrane-embedded receptor.(omitted)

  • PDF

Control of Platelet Rolling and Adhesion

  • Moskowitz, Samuel E.
    • 제어로봇시스템학회:학술대회논문집
    • /
    • 제어로봇시스템학회 2002년도 ICCAS
    • /
    • pp.77.1-77
    • /
    • 2002
  • Platelets arrest bleeding and repair damaged blood vessels. The purpose of this paper is to formulate a mathematical model for the control of platelet adhesion within the vasculature consistent with experimental findings, particularly those of Frenette, Ruggeri , Savage, Yuan, Lawrence and Springer. In addition to providing some, albeit rudimentary, insight into the behavior of platelets, a numerical simulation of this theoretical model may be useful in a systematic study of pathological cases. Glycoprotein receptor complex (GPIb/V/IX), found on the platelet surface membrane, binds to the adhesive protein and ligand von Willebrand factor (vWf), located within the sub-endothelium. The binding...

  • PDF

Anti-atherogenic Effect of Tilianin from Agastache rugosa

  • Lee, Hyeong-Kyu;Oh, Sei-Ryung;Oh, Goo-Taeg
    • 대한약학회:학술대회논문집
    • /
    • 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-1
    • /
    • pp.64-65
    • /
    • 2003
  • Investigation of immunomodulating activities of the Agastache rugosa (Bae-cho-hyang) extract and its components was preformed through screening in vitro assays and evaluating anti-inflammatory activity and anti-atherosclerotic activity of the extract and tilianin in vivo. The extract showed strong anti-inflammatory activity in carrageenan-induced acute edema mouse model and anti-atherogenic activity in LDLR (low density lipoprotein receptor) deficient mouse model. (omitted)

  • PDF

서울지역에서의 VOCs 오염원 기여도 추정에 관한 연구 (Estimation of Quantitative Source Contribution of VOCs in Seoul Area)

  • 봉춘근;윤중섭;황인조;김창녕;김동술
    • 한국대기환경학회지
    • /
    • 제19권4호
    • /
    • pp.387-396
    • /
    • 2003
  • A field study was conducted during the summer time of 2002 to determine compositions of volatile organic compounds (VOCs) emitted from vehicles and to develop source emission profiles that is applied to CMB model to estimate the source contribution of certain area. Source emission profile is widely used for the estimation of source contribution by the chemical mass balance model and have to be developed applicable for the target area of estimation. This study was aimed to develop source emission profile and estimation of source contribution of VOCs after application of the chemical mass balance (CMB) receptor model. After considering the emission inventory and other research results for the VOCs in Seoul, Korea, the sources like vehicle emission (tunnel), gas station (gasoline, diesel), solvent usage (painting operation, dry cleaning, graphic art), and gas fuels were selected for the major VOCs sources. Furthermore, ambient air samples were simultaneously collected from 09:00 to 11:00 for four days at eight different official air quality monitoring sites as receptors in Seoul during summer of 2001. Source samples were collected by canisters, and then about seventy volatile organic compounds were analyzed by gas chromatography with flame ionization detector (GC/FID). Based on both the developed source profiles and the database of the receptors, CMB model was intensively applied to estimate mass contribution of VOCs sources. Examining the source profile from the vehicle, the portion of alkanes of VOCs was highest, and then the portion of aromatics such toluene, m/p-xylene were followed. In case of gas fuel. they have their own components; the content of butane, propane, ethane was higher than any other component according to the fuel usage. The average of the source apportionment on VOCs for 8 sites showed that the major sources were vehicle emission and gas fuels. The vehicle emission source was revealed as having the highest contribution with an average of 49.6%, and followed by solvent with 21.3%, gas fuel with 16.1%, gasoline with 13.1%.

Developmental Disability Animal Model Based on Neonatal Lipopolysaccharide with Altered 5-HT Function

  • Kim, Jae-Goo;Kim, Min-Soo;Lee, Se-Oul;Kim, Gun-Tae;Lee, Jong-Doo;Kim, Dong-Goo
    • The Korean Journal of Physiology and Pharmacology
    • /
    • 제11권3호
    • /
    • pp.113-119
    • /
    • 2007
  • Developmental disability shows life-long behavioral abnormality with no significant physical malformation. This study was undertaken to develop an animal model for developmental disability by using two-factor approach. Lipopolysaccharide (LPS), a bacterial toxin, and NAN-190, a $5-HT_{1A}$ receptor antagonist, were administered to Sprague-Dawley rats on postnatal day (PND) 5 to induce inflammation and an altered 5-HT system, respectively. Long-term alteration of behavior occurred in the drug-treated groups. The LPS-treated group showed impaired motor coordination in the Rota-rod test. The LPS- treated or both LPS and NAN-190-treated groups showed impaired fore-paw muscle power in the wire maneuver test. These groups also showed decreased white matter volume and increased serotonergic fibers. The LPS and NAN-190-treated group also exhibited neurologic deficit in the placing reaction test and impaired equilibrium function in the tilt table test. The results showed that a variety of altered behaviors can be generated by two factor model, and suggested that combination of important etiologic factors and possible underlying defects is a promising strategy of establishing an animal model for developmental disabilities.

Anti-nociceptive effects of dual neuropeptide antagonist therapy in mouse model of neuropathic and inflammatory pain

  • Kim, Min Su;Kim, Bo Yeon;Saghetlians, Allen;Zhang, Xiang;Okida, Takuya;Kim, So Yeon
    • The Korean Journal of Pain
    • /
    • 제35권2호
    • /
    • pp.173-182
    • /
    • 2022
  • Background: Neurokinin-1 (NK1) and calcitonin gene-related peptide (CGRP) play a vital role in pain pathogenesis, and these proteins' antagonists have attracted attention as promising pharmaceutical candidates. The authors investigated the anti-nociceptive effect of co-administration of the CGRP antagonist and an NK1 antagonist on pain models compared to conventional single regimens. Methods: C57Bl/6J mice underwent sciatic nerve ligation for the neuropathic pain model and were injected with 4% formalin into the hind paw for the inflammatory pain model. Each model was divided into four groups: vehicle, NK1 antagonist, CGRP antagonist, and combination treatment groups. The NK1 antagonist aprepitant (BIBN4096, 1 mg/kg) or the CGRP antagonist olcegepant (MK-0869, 10 mg/kg) was injected intraperitoneally. Mechanical allodynia, thermal hypersensitivity, and anxiety-related behaviors were assessed using the von Frey, hot plate, and elevated plus-maze tests. The flinching and licking responses were also evaluated after formalin injection. Results: Co-administration of aprepitant and olcegepant more significantly alleviated pain behaviors than administration of single agents or vehicle, increasing the mechanical threshold and improving the response latency. Anxiety-related behaviors were also markedly improved after dual treatment compared with either naive mice or the neuropathic pain model in the dual treatment group. Flinching frequency and licking response after formalin injection decreased significantly in the dual treatment group. Isobolographic analysis showed a meaningful additive effect between the two compounds. Conclusions: A combination pharmacological therapy comprised of multiple neuropeptide antagonists could be a more effective therapeutic strategy for alleviating neuropathic or inflammatory pain.

LDL Receptor Knockout Mouse에서 부추추출물의 죽상경화증 예방 효과 (Prevention effect of Allium tuberosum extract on ateriosclerosis in LDL Receptor Knockout Mouse)

  • 권오준;이주영;노성수
    • 대한본초학회지
    • /
    • 제31권2호
    • /
    • pp.13-19
    • /
    • 2016
  • Objectives : The present study was designed to evaluate the protective effect of Allium tuberosum (AT) extract on atherosclerosis in LDL receptor knockout (LDLr KO) mouse fed western diet.Methods : The AT was extracted 70% ethanol. The experimental groups were divided with four groups of LDLr KO mice, one group fed a normal diet and the others fed a Western diets for 8weeks. Two Western diet groups were orally administered AT extract at dosage of 100 and 300 mg/kg body weight. The body weight and food intake were measured every day. We measured levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride (TG), total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and Glucose in serum. Also, effect of AT extract performed using H&E staining.Results : The AT treatment groups showed decrease in body weight and food efficiency in comparison with control group. Blood biochemistry parameters such as TG, TC, LDL, and glucose levels were increased in control group, while AT treatment groups were reduced. Also, the increased levels of ALT and AST were improved by AT extract. We confirmed that the weights of liver, kidney, subcutaneous fat, epididymal fat, kidney leaf fat, and intraabdominal fat were change in LDLr KO mice treated AT extract. In addition, histopathological changes in liver and aorta were similar to normal group.Conclusions : Based on these results, the AT extract is considered to make prevention of atherosclerosis through reduction and functional improvement of the liver and vascular endothelial cells in the body fat accumulation and lipid content in LDLr ko mouse model.