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Involvement of Age-associated Golgi Stress in Impairment of Nuclear Translocation
| DC Field | Value | Language |
|---|---|---|
| dc.contributor.advisor | Bum-Ho Bin | - |
| dc.contributor.author | ANA SOFIA PEREIRA DE BRITO | - |
| dc.date.accessioned | 2022-11-29T03:01:25Z | - |
| dc.date.available | 2022-11-29T03:01:25Z | - |
| dc.date.issued | 2022-08 | - |
| dc.identifier.other | 32242 | - |
| dc.identifier.uri | https://dspace.ajou.ac.kr/handle/2018.oak/21152 | - |
| dc.description | 학위논문(박사)--아주대학교 일반대학원 :응용생명공학과,2022. 8 | - |
| dc.description.tableofcontents | 1. Introduction 1 1.1. The senescent cell 1 1.2. The Golgi apparatus during aging 4 1.3. Zinc deficiency in aging 7 1.4. Research objectives 10 2. Experimental Methods 11 2.1. Cell culture and materials 11 2.2. Animal experiments 11 2.3. Western blot 11 2.4. BODIPY staining for flow cytometry 12 2.5. Immunofluorescence staining of cells 12 2.6. Immunoprecipitation 13 2.7. Isolation of Golgi-microtubule complexes 13 2.8. Nuclear and perinuclear fractionation 14 2.9. Tissue sampling 14 2.10. Cytosolic and nuclear fraction 14 2.11. Plasmid transfection 15 2.12. Real time quantitative polymerase chain reaction (qPCR) 15 2.13. Statistical analysis 15 3. Results 16 3.1. Aging led to an increase in Golgi stress 16 3.2. Aging disturbed Golgi structure and stacking 18 3.3. Golgi stress disturbed Golgi-derived microtubule assembly 20 3.4. Golgi stress impaired Golgi MT-mediated protein nuclear translocation 22 3.5. Golgi stress reduced the expression of hepatic zinc importer ZIP14 24 3.6. Zinc deficiency accelerated Golgi stress by inhibiting Golgi stacking 26 3.7. Zinc deficiency led to microtubule dysfunction 28 3.8. Zinc deficiency disturbed microtubule-mediated cellular signaling and epigenetic regulation 30 4. Discussion 33 5. Conclusions and Future Perspectives 38 6. References 39 7. Supplemental Information 47 | - |
| dc.language.iso | eng | - |
| dc.publisher | The Graduate School, Ajou University | - |
| dc.rights | 아주대학교 논문은 저작권에 의해 보호받습니다. | - |
| dc.title | Involvement of Age-associated Golgi Stress in Impairment of Nuclear Translocation | - |
| dc.type | Thesis | - |
| dc.contributor.affiliation | 아주대학교 일반대학원 | - |
| dc.contributor.department | 일반대학원 응용생명공학과 | - |
| dc.date.awarded | 2022. 8 | - |
| dc.description.degree | Doctoral | - |
| dc.identifier.localId | T000000032242 | - |
| dc.identifier.uci | I804:41038-000000032242 | - |
| dc.identifier.url | https://dcoll.ajou.ac.kr/dcollection/common/orgView/000000032242 | - |
| dc.subject.keyword | Ajou | - |
| dc.subject.keyword | thesis | - |
| dc.description.alternativeAbstract | In light of the increase in human life span, we are now faced with the task of not only increasing longevity but also boosting health span as we age. Cellular senescence is a key feature of aging that contributes to age-related illnesses and is also a viable therapeutic target. Furthermore, recent reports have demonstrated that senescence leads to inhibition of cytoplasm to nucleus nuclear translocation, but these mechanisms are yet far from being well understood. The Golgi apparatus is a stacked membrane organelle in the perinuclear region that functions as a center for protein and lipid trafficking as well as post-translational modifications of cargoes prior to delivery to their final destinations. However, it is not yet well understood how the Golgi apparatus changes during aging. Here, we found that the Golgi apparatus and Golgi-derived microtubules (Golgi MTs) are required for correct nuclear translocation of proteins for the regulation of cellular signaling and epigenetics. Furthermore, we reveal that age-related zinc deficiency elevates Golgi stress preventing the proper function of zinc-dependent stacking proteins on the Golgi-cisternal membrane. In addition, zinc deficiency also reduces Golgi-bound microtubule structures and induces defects on nuclear translocation of proteins in aged cells. Thus, we claim that zinc deficiency during aging produces a positive feedback loop with the disturbed Golgi apparatus, worsening fragmentation and exacerbating the aging phenotype. Our findings propose an explanation for why aged cells are less receptive to stimulation and highlight the importance of a proper zinc diet during aging. | - |
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- Graduate School of Ajou University > Department of Applied Biotechnology > 4. Theses(Ph.D)
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