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| DC Field | Value | Language |
|---|---|---|
| dc.contributor.advisor | 김경민 | - |
| dc.contributor.author | 송찬호 | - |
| dc.date.issued | 2024-08 | - |
| dc.identifier.other | 33911 | - |
| dc.identifier.uri | https://aurora.ajou.ac.kr/handle/2018.oak/39148 | - |
| dc.description | 학위논문(석사)--의생명과학과,2024. 8 | - |
| dc.description.abstract | Sirtuin Family의 일원인 Sirtuin 5 (SIRT5)는 주로 미토콘드리아에 존재하여, desuccinylase와 demalonylase 활동을 통해 세포 내에서 발생하는 다양한 대사 반응을 조절합니다. 즉, SIRT5는 세포의 에너지 생산 및 대사 조절에 중요한 영향을 미친다고 알려져 있습니다. B형 간염 바이러스 (hepatitis B virus, HBV) 증식에 대한 SIRT5의 효소 작용 효과는 아직 밝혀지지 않았습니다. 본 연구에서 저는 HBV가 증식하는 세포에서는 endogenous SIRT5가 감소한다는 것을 발견했습니다. SIRT5 Isoform 1 (SIRT5.1)를 과발현하면 HBV mRNA 전사 및 replicative intermediate (RI) DNA 합성이 감소됨과 동시에 AMPK (AMP-activated protein kinase)가 활성화되고 AKT (protein kinase B) 신호 전달 경로가 억제됩니다. 또한, AMPK를 과발현하면 SIRT5 활성화를 통해 AKT 신호 전달 경로를 억제하고 HBV mRNA 및 RI DNA를 감소시켰습니다. 이러한 결과는 HBV 증식이 SIRT5 활성을 억제하고, SIRT5.1 과발현이 AMPK 및 AKT신호 전달 경로를 통해 HBV 증식을 억제한다는 것을 보여줍니다. 따라서 SIRT5.1의 과발현은 HBV 감염에 대한 새로운 치료 표적이 될 수 있습니다._x000D_ <br>핵심어 : B형 간염 바이러스, B형 간염 바이러스 증식, SIRT5, SIRT5 Isoform 1, AMPK, AKT|Sirtuin 5 (SIRT5), a member of the Sirtuin family, is primarily localized in the mitochondria and regulates various cellular metabolic reactions through its desuccinylase and demalonylase activities. It is known that SIRT5 significantly influences cellular energy production and metabolic control. However, the effect of SIRT5's enzymatic activity on hepatitis B virus (HBV) replication has never been explored. In this study, I discovered that endogenous SIRT5 level is decreased by HBV replication. Overexpression of SIRT5 Isoform 1 (SIRT5.1) results in a reduction of HBV mRNA transcription and replicative intermediate (RI) DNA synthesis, along with the activation of AMP-activated protein kinase (AMPK) and inhibition of the AKT (protein kinase B) signaling pathway. Additionally, AMPK overexpression was found to activate SIRT5, leading to suppression of AKT signaling pathway and a decrease in HBV mRNA and RI DNA levels. These findings suggest that HBV replication suppresses SIRT5 activity, while SIRT5.1 overexpression inhibits HBV replication through the AMPK and AKT signaling pathways. Therefore, SIRT5.1 overexpression could be a potential therapeutic target for HBV infection._x000D_ <br>Keywords : HBV, HBV replication, SIRT5, SIRT5 Isoform 1, AMPK, AKT | - |
| dc.description.tableofcontents | Ⅰ. 서론 1_x000D_ <br>Ⅱ. 실험 재료 및 방법 5_x000D_ <br> A. DNA Constructs 5_x000D_ <br> B. Cell Culture 6_x000D_ <br> C. Transfection 7_x000D_ <br> D. SDS-PAGE and Western Blotting 8_x000D_ <br> E. Core particle Immunoblotting 11_x000D_ <br> F. Northern and Southern Blotting 12_x000D_ <br> G. Co-Immunoprecipitation 13_x000D_ <br> H. Statistical Analysis 14_x000D_ <br>Ⅲ. 결과 15_x000D_ <br> A. HBV 증식 세포에서 endogenous SIRT5 발현 감소 15_x000D_ <br> B. HBV 관련 HCC 환자에서의 SIRT5 발현 및 수준 변화 19_x000D_ <br> C. SIRT5.1 과발현에 의한 HBV 증식 억제 22_x000D_ <br> D. SIRT5.1 WT 과발현과 달리 catalytically inactive mutant (H158Y) 과발현은 HBV 증식을 억제하지 못함 27_x000D_ <br> E. SIRT5.1 과발현은 AMPK 활성화 유도하여 HBV 증식을 억제함 32_x000D_ <br> F. AMPK 과발현으로 SIRT5 가 증가되어 HBV 증식이 억제됨 38_x000D_ <br> G. 면역침강법을 통한 SIRT5.1 과 AMPK 의 상호작용규명 43_x000D_ <br>Ⅳ. 고찰 47_x000D_ <br>Ⅴ. 결론 50_x000D_ <br>참고문헌 51_x000D_ <br>ABSTRACT 59_x000D_ | - |
| dc.language.iso | kor | - |
| dc.publisher | The Graduate School, Ajou University | - |
| dc.rights | 아주대학교 논문은 저작권에 의해 보호받습니다. | - |
| dc.title | Sirtuin 5 Isoform 1이 B형 간염 바이러스 증식에 미치는 영향 | - |
| dc.title.alternative | Sirtuin 5 Isoform 1 inhibits Hepatitis B virus Replication | - |
| dc.type | Thesis | - |
| dc.contributor.affiliation | 아주대학교 대학원 | - |
| dc.contributor.alternativeName | Chanho Song | - |
| dc.contributor.department | 일반대학원 의생명과학과 | - |
| dc.date.awarded | 2024-08 | - |
| dc.description.degree | Master | - |
| dc.identifier.url | https://dcoll.ajou.ac.kr/dcollection/common/orgView/000000033911 | - |
| dc.subject.keyword | AKT | - |
| dc.subject.keyword | AMPK | - |
| dc.subject.keyword | B형 간염 바이러스 | - |
| dc.subject.keyword | B형 간염 바이러스 증식 | - |
| dc.subject.keyword | SIRT5 | - |
| dc.subject.keyword | SIRT5 Isoform 1 | - |
| dc.description.alternativeAbstract | Sirtuin 5 (SIRT5), a member of the Sirtuin family, is primarily localized in the mitochondria and regulates various cellular metabolic reactions through its desuccinylase and demalonylase activities. It is known that SIRT5 significantly influences cellular energy production and metabolic control. However, the effect of SIRT5's enzymatic activity on hepatitis B virus (HBV) replication has never been explored. In this study, I discovered that endogenous SIRT5 level is decreased by HBV replication. Overexpression of SIRT5 Isoform 1 (SIRT5.1) results in a reduction of HBV mRNA transcription and replicative intermediate (RI) DNA synthesis, along with the activation of AMP-activated protein kinase (AMPK) and inhibition of the AKT (protein kinase B) signaling pathway. Additionally, AMPK overexpression was found to activate SIRT5, leading to suppression of AKT signaling pathway and a decrease in HBV mRNA and RI DNA levels. These findings suggest that HBV replication suppresses SIRT5 activity, while SIRT5.1 overexpression inhibits HBV replication through the AMPK and AKT signaling pathways. Therefore, SIRT5.1 overexpression could be a potential therapeutic target for HBV infection._x000D_ <br>Keywords : HBV, HBV replication, SIRT5, SIRT5 Isoform 1, AMPK, AKT | - |
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