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Honokiol attenuates angiotensinⅡ-induced hypertensin by inhibiting HDAC6-mediated cystathionine γ-lyase degradation
| DC Field | Value | Language |
|---|---|---|
| dc.contributor.advisor | 이숙영 | - |
| dc.contributor.author | CHI ZHEXI | - |
| dc.date.accessioned | 2022-11-29T02:32:43Z | - |
| dc.date.available | 2022-11-29T02:32:43Z | - |
| dc.date.issued | 2021-02 | - |
| dc.identifier.other | 30691 | - |
| dc.identifier.uri | https://dspace.ajou.ac.kr/handle/2018.oak/20286 | - |
| dc.description | 학위논문(박사)--아주대학교 일반대학원 :의학과,2021. 2 | - |
| dc.description.tableofcontents | I. INTRODUCTION 1 II. MATERIALS AND METHODS 5 1. Chemicals 5 2. AngII-infused hypertensive mice and HNK injection 5 3. Blood pressure measurement 6 4. Force tension myography 6 5. Cell cultures and treatments 7 6. H2S measurement 8 7. Antibodies and plasmids 9 8. Transfection and gene knockdown 9 9. Western blotting and immunoprecipitation (IP) 10 10. HNK–HDAC6 binding 10 11. HDAC6 activity assay 11 12. Statistical analysis 11 III. RESULTS 13 1. HNK attenuates AngII-induced hypertension and vascular endothelial dysfunction 13 2. HNK recovers H2S levels decreased by AngII 18 3. HNK increases CSE protein levels by enhancing its stability against proteasomal degradation 22 4. HNK-mediated HDAC6 inhibition induces CSE acetylation, which contributes to CSE Uregulation 29 5. CSE acetylation at K73 prevents its degradative ubiquitination 41 IV. DISCUSSION 49 V. CONCLUSION 54 REFERENCES 55 국문요약 65 | - |
| dc.language.iso | eng | - |
| dc.publisher | The Graduate School, Ajou University | - |
| dc.rights | 아주대학교 논문은 저작권에 의해 보호받습니다. | - |
| dc.title | Honokiol attenuates angiotensinⅡ-induced hypertensin by inhibiting HDAC6-mediated cystathionine γ-lyase degradation | - |
| dc.title.alternative | Honokiol은 HDAC6 에 의한 cystathionine γ-lyase의 분해를 억제하여 angiotensin Ⅱ 유도 고혈압 진행을 완화한다 | - |
| dc.type | Thesis | - |
| dc.contributor.affiliation | 아주대학교 일반대학원 | - |
| dc.contributor.department | 일반대학원 의학과 | - |
| dc.date.awarded | 2021. 2 | - |
| dc.description.degree | Doctoral | - |
| dc.identifier.localId | 1218622 | - |
| dc.identifier.uci | I804:41038-000000030691 | - |
| dc.identifier.url | http://dcoll.ajou.ac.kr:9080/dcollection/common/orgView/000000030691 | - |
| dc.subject.keyword | acetylation | - |
| dc.subject.keyword | angiotensin II | - |
| dc.subject.keyword | cystathionine γ-lyase | - |
| dc.subject.keyword | histone deacetylase 6 | - |
| dc.subject.keyword | honokiol | - |
| dc.subject.keyword | hydrogen sulfide | - |
| dc.subject.keyword | hypertension | - |
| dc.description.alternativeAbstract | Hypertension and endothelial dysfunction are associated with various cardiovascular diseases. Cystathionine γ-lyase (CSE) is an enzyme that produces hydrogen sulfide (H2S). Endothelial H2S production promotes vascular relaxation, supporting to the alleviation of hypertension. Honokiol (HNK) is a natural compound in the Magnolia plant, has been shown to retain multifunctional attributes such as anti-oxidant and anti-inflammatory activity. However, a potential role of HNK in mediating CSE and hypertension remains mostly unknown. Here, We directed to indicate that HNK cotreatment attenuated the hypertension, vasoconstriction, and H2S reduction caused by angiotensin II (AngII), a well-induced inducer of hypertension. Recent studies the part of histone deacetylase 6 (HDAC6) in hypertension has been recommend, but the underlying mechanisms are poorly understood. We found that tubastatin A the HDAC6 inhibitor attenuates angiotensin II induced hypertension by preventing CSE protein degradation. Our results indicate that HNK could improve CSE acetylation levels by inhibiting HDAC6 catalytic activity, By blocking the AngII-induced degradative ubiquitination of CSE. CSE acetylation and ubiquitination happened mainly on the lysine 73 (K73) residue. Conversely, its mutant (K73R) was against to both acetylation and ubiquitination, expressing higher protein stability than that of wild-type CSE. Overall, this study recommend that HNK treatment protects CSE against HDAC6-mediated degradation and may comprise an alternative for preventing endothelial dysfunction and hypertension. | - |
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- Graduate School of Ajou University > Department of Medicine > 4. Theses(Ph.D)
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