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The Roles of Sirtuin5 Isoform1 on Hepatitis B Virus Replication
| DC Field | Value | Language |
|---|---|---|
| dc.contributor.advisor | Kyongmin Kim | - |
| dc.contributor.author | FADIA KALSOOM | - |
| dc.date.accessioned | 2022-11-29T03:01:03Z | - |
| dc.date.available | 2022-11-29T03:01:03Z | - |
| dc.date.issued | 2022-02 | - |
| dc.identifier.other | 31516 | - |
| dc.identifier.uri | https://dspace.ajou.ac.kr/handle/2018.oak/20694 | - |
| dc.description | 학위논문(석사)--아주대학교 일반대학원 :의생명과학과,2022. 2 | - |
| dc.description.tableofcontents | 1. Introduction 1 2. Material and methods 4 2.1. Vector construct 4 2.2 Transfection and cell line culture 6 2.3 Core particle and immuno-blotting 7 2.4 Northern and southern blotting 8 2.5 SDS-PAGE and Western blotting 9 2.6 Total, cytoplasmic, nuclear, mitochondrial fractionations 10 3. Results 11 3.1 SIRT5 expression in HCC is associated with HBV infection 11 3.2 Isoforms of SIRT5 14 3.3 Subcellular localization of SIRT5.1 and SIRT5.4 17 3.4 HBV replication down regulates the endogenous SIRT5.1 protein expression 20 3.5 Overexpression of SIRT5.1 downregulates HBV replication and HBV RNAs 23 3.6 Effect of overexpression of SIRT5.1 (H158Y) catalytically inactive mutant on HBV replication and HBV RNAs 26 3.7 SIRT5.1 act as up regulator of AMPK for restricting HBV replication 29 3.8 AMPK act as up-regulator of SIRT5.1 for restricting HBV replication 32 4. Discussion 35 5. References 37 | - |
| dc.language.iso | eng | - |
| dc.publisher | The Graduate School, Ajou University | - |
| dc.rights | 아주대학교 논문은 저작권에 의해 보호받습니다. | - |
| dc.title | The Roles of Sirtuin5 Isoform1 on Hepatitis B Virus Replication | - |
| dc.type | Thesis | - |
| dc.contributor.affiliation | 아주대학교 일반대학원 | - |
| dc.contributor.department | 일반대학원 의생명과학과 | - |
| dc.date.awarded | 2022. 2 | - |
| dc.description.degree | Master | - |
| dc.identifier.localId | 1245118 | - |
| dc.identifier.uci | I804:41038-000000031516 | - |
| dc.identifier.url | https://dcoll.ajou.ac.kr/dcollection/common/orgView/000000031516 | - |
| dc.subject.keyword | HBV replication | - |
| dc.subject.keyword | SIRT5.1 | - |
| dc.subject.keyword | SIRT5.1 (H158Y mutant) | - |
| dc.subject.keyword | SIRT5.4 | - |
| dc.description.alternativeAbstract | Hepatitis B virus is a small DNA virus constituent of the Hepadnaviridae family having a genome size of 3.2 kb. HBV infected, with the exception of 296 million people worldwide chronically. Hepatocellular carcinoma (HCC) is a chronic liver disease associated with numerous complications, among other causes chronic hepatitis B virus (HBV) infection is a major cause of HCC. Varieties of liver defects are associated with Sirtuins via deacetylation. Sirtuins are a family of NAD+-dependent protein lysine deaceylases that are involved in the regulation of a diverse range of physiological processes and SIRT5 is affiliated with this family. SIRT5 is acclaimed for its thriving activities like lysine-demalonylase, desuccinylase, deglutarylation, deacetylase, deglutarylase, and demyristoylase and these activities modulate a variety of enzymes involved in cellular metabolism and post-translational modifications. SIRT5 also has ability to produce anti-RNA and DNA virus innate immune response. The research just has begun in the recent past about the involvement of SIRT5.1 in HCC. Nonetheless, there are not so far any conclusions yielded on whether SIRT5 has a positive or negative impact in HCC, despite the fact that it is indicated at only low levels in tumor specimens. I investigated that whether there is any role of SIRT5 in HBV replication and I tried to find out any change in expression of SIRT5 affects the HBV replication. Out of eight isoforms of SIRTs I worked on two isoforms SIRT5.1 and SIRT5.4 I found that in HBV replicating cells the overexpression of SIRT5.1 reduced the replicative intermediate DNAs expression of HBV mRNAs in HepG2 and Huh7 cells. On the contrary SIRT5.4, N-terminally truncated Variant has no significant effect on the HBV life cycle. The SIRT5.1 was mainly found to localize in mitochondria whereas its localization was also seen in the nucleus and cytoplasm. Furthermore, the endogenous expression level of SIRT5.1 was found significantly decreased in three liver cell lines (Huh7, HepG2, and HepAD38). SIRT5 protein level in biopsied HBV-associated liver tissues and I found that SIRT5 expressed lower than the adjacent non-tumor tissues. I constructed SIRT5.1 catalytically inactive mutant H158Y as expected the catalytically inactive mutant H158Y has not shown the significant effect on HBV replication and HBV mRNAs. In this research I have tried to find out the role of SIRT5.1 on HBV replication and interplay of AMPK and SIRT5.1 in restriction of HBV, because it is already published that AMPK is a down-regulator of HBV. I found that HBV replication down regulated when SIRT5.1 is overexpressed and SIRT5.1 has up-regulating effect on AMPK activation so we can say that SIRT5.1 participates in the same pathway that leads to autophagy-related restriction of HBV. In future, I have planned to find out the underlying mechanism of how SIRT5.1 decreases HBV replication by interacting with AMPK in detail. Collectively, my research braces additional investigations of SIRT5 as a therapeutic target. It can help in revealing new approach to controlling HBV on the molecular level. | - |
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