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Effects of asaronic acid on phenotypes and unfolded protein degradation in various stress-loaded macrophages = 다양한 스트레스에 노출된 대식세포의 형태와 미접힘단백질 분해에 대한 아사론산의 영향

저자 : 오형주

발행사항 : 춘천 : 한림대학교 일반대학원, 2021

학위논문사항 : 학위논문(박사)-- 한림대학교 일반대학원 : 식품영양학과 2021. 8

발행연도 : 2021

작성언어 : 한국어

주제어 : 아사론산 ,대식세포 ,대식세포분극 ,소포체관련단백질분해

발행국(도시) : 강원도

형태사항 : 112 p ; 26 cm

일반주기명 : 지도교수: 강영희

소장기관 :

  • 한림대학교 도서관

서지정보 열기
    원문보기 내보내기 내서재담기 한글로보기
  • 국문 초록 (Abstract)
  • 번역
  • 번역결과

    한글번역보기는 자동번역 서비스로 원문과 일부 불일치할 수 있으며, 번역물과 관련하여 어떠한 법적 책임도 지지 않습니다.

  • 목차
    • Chapter 1 ··········································································································································································1
    • Asaronic acid attenuates macrophage activation toward M1 phenotype through inhibition of NF-κB pathway and JAK-STAT signaling in glucose-loaded murine macrophages
    • 1.1. Introduction ··············································································································································2
    • 1.2. Materials and Methods ·····························································································································5
    • 1.2.1. Chemical ················································································································································5
    • 1.2.2. Cell culture ·············································································································································5
    • 1.2.3. Enzyme-linked Immunosorbent Assay (ELISA) ·······················································································6
    • 1.2.4. Western blot ··········································································································································6
    • 1.2.5. Immunocytochemical Analysis ···············································································································7
    • 1.2.6. Data Analysis ··········································································································································8
    • 1.3. Results ·······················································································································································9
    • 1.3.1. Suppression of LPS-induced inflammation by Asaronic acid ··································································9
    • 1.3.2. Inhibition of TLR4-Mediated M1 Macrophage Activation by Asaronic acid ···········································11
    • 1.3.3. Blockade of LPS-Induced Activation of NF-κB and STAT signaling by Asaronic acid ·······························13
    • 1.3.4. Inhibitory Effects of Asaronic acid on Inflammation of HIF-1α-VEGF ·····················································15
    • 1.3.5. Disturbance of glucose-triggered STAT signaling by Asaronic acid·························································20
    • 1.4. Discussion···················································································································································23
    • 1.5. Conclusion ·················································································································································27
    • 1.6. References ·················································································································································28
    • Chapter 2 ··························································································································································34
    • Asaronic acid inhibited glucose-triggeredM2-phenotype shift through disrupting the formation of coordinated signaling of IL4Rα-Tyk2-STAT6 and GLUT1-Akt-mTOR-AMPK
    • 2.1. Introduction ···············································································································································35
    • 2.2. Materials and methods ······························································································································38
    • 2.2.1. Materials ·················································································································································38
    • 2.2.2. Cell culture ·············································································································································39
    • 2.2.3. Western blot analysis ······························································································································40
    • 2.2.4. Enzyme-linked immunosorbent assay (ELISA) ························································································40
    • 2.2.5. Immunocytochemical analysis ·················································································································41
    • 2.2.6. Dihydroethidium (DHE) staining for ROS production ··············································································41
    • 2.2.7. Data analysis ···········································································································································41
    • 2.3. Results ························································································································································43
    • 2.3.1. IL-4-mediated IL-4Rα induction by Asaronic acid ····················································································43
    • 2.3.2. IL-4-mediated M2 macrophage activation by Asaronic acid ···································································45
    • 2.3.3. Angiogenic and proliferative capacity of Asaronic acid n M2-polarized macrophages ··························47
    • 2.3.4. Effects of Asaronic acid on IL-4-mediated M2 macrophage metabolism ···············································49
    • 2.3.5. Inhibition of glucose-triggered M2 macrophage activation by Asaronic acid ·········································51
    • 2.3.6. Glucose-triggered metabolic alterations in M2 macrophages ································································56
    • 2.3.7. Blockade of diabetic M2 macrophage dysfunction by Asaronic acid ······················································58
    • 2.4. Discussion···················································································································································61
    • 2.5. Conclusion ·················································································································································67
    • 2.6. Reference ···················································································································································68
    • Chapter 3···························································································································································76
    • Asaronic acid inhibits ER stress sensors and boosts functionality of ubiquitin-proteasomal degradation in 7ꞵhydroxycholesterol-loaded macrophages
    • 3.1. Introduction ··············································································································································77
    • 3.2. Methods and materials ·····························································································································80
    • 3.2.1. Materials ················································································································································80
    • 3.2.2. Cell culture ·············································································································································80
    • 3.2.3. Western blot analysis ·····························································································································81
    • 3.2.4. Immunocytochemical staining ···············································································································82
    • 3.2.5. Data analysis ··········································································································································82
    • 3.3. Results ······················································································································································83
    • 3.3.1. Blockade of 7β-hydroxycholesterol-induced ERstress sensors by asaronic acid······································83
    • 3.3.2. Inhibition of EDEM1 and OS9 for initial recognition by asaronic acid ···················································85
    • 3.3.3. Suppression of Sel1L and Hrd1 by asaronic acid ···················································································87
    • 3.3.4. Modulation of ubiquitination-related chaperones by asaronic acid·······················································89
    • 3.3.5. Effects of Asaronic acid on ubiquitination ····························································································91
    • 3.3.6. Effects of Asaronic acid on proteasomal degradation ··········································································93
    • 3.4. Discussion·················································································································································97
    • 3.5. Conclusion ··············································································································································101
    • 3.6. References ··············································································································································102
    • 국문초록 ··························································································································································109
    • Abstract···························································································································································111