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Biological and Molecular Characteristics of Senescent Melanocytes
| DC Field | Value | Language |
|---|---|---|
| dc.contributor.advisor | 강희영 | - |
| dc.contributor.author | 이진욱 | - |
| dc.date.accessioned | 2022-11-29T03:01:22Z | - |
| dc.date.available | 2022-11-29T03:01:22Z | - |
| dc.date.issued | 2022-08 | - |
| dc.identifier.other | 32209 | - |
| dc.identifier.uri | https://dspace.ajou.ac.kr/handle/2018.oak/21089 | - |
| dc.description | 학위논문(박사)--아주대학교 일반대학원 :의학과,2022. 8 | - |
| dc.description.abstract | 연구배경: 노화 멜라닌세포는 나이가 들면서 증가하며 노화과정에 역할을 한다. 연구목적: 본 연구는 노화 멜라닌세포의 분자생물학적인 특징을 연구하고자 하였다. 연구방법: 두개의 in vitro 멜라닌세포 노화모델을 구축하였으며 노화 멜라닌세포의 특징을 알아보기 위하여 멜라닌생성과정, 멜라닌소체의 이동, 자가포식 등에 관여하는 분자들을 분석하였다. 연구결과: 각각의 모델에서 멜라닌세포의 노화정도는 senescence-associated β-galactosidase (SA-β-Gal)의 활성도와 노화표지자인 p16INK4a의 발현을 측정하여 확인하였다. 노화 멜라닌세포에서 p16INK4a 발현이 증가되어 있으며 SA-β-Gal 양성 세포들이 많이 관찰되었다. 총멜라닌양은 증가되어 있었으나 티로시나아제의 활성도 및 MITF 전사요소 발현정도와는 상관관계가 없었다. 멜라닌소체의 이동에 관여하는 ras-related protein Rab-27A, melanophilin, and myosin-Va의 발현 정도는 감소되어 있었다. 이는 노화 멜라닌세포에서 멜라닌소체의 이동에 결함이 있음을 시사한다. 또한 노화 멜라닌세포에서 자가포식의 기능이 감소되어 있는 것을 확인하였으며, 자가포식 기능에 관여하는 Microtubule-associated protein 1 light chain 3 (LC3)-II, Beclin 1, Autophagy related 5 (ATG5)가 감소되어 있었다. 결론: 노화 멜라닌 세포는 멜라닌색소의 정체가 특징적으로 나타나며 멜라닌소체의 이동 결함 및 자가포식기능의 장애를 보인다. | - |
| dc.description.tableofcontents | INTRODUCTION 1 MATERIAL AND METHODS 6 1. Cell culture and UVB irradiation 6 2. Senescence Associated β-Galactosidase (SA-β-Gal) Staining 6 3. Melanin content and tyrosinase activity assay 6 4. Real-time polymerase chain reaction (PCR) analysis 7 5. Western blot analysis 7 6. RNA sequencing 8 7. Statistical analysis 8 RESULTS 9 DISCUSSION 17 CONCLUSION 22 REFERENCES 23 | - |
| dc.language.iso | eng | - |
| dc.publisher | The Graduate School, Ajou University | - |
| dc.rights | 아주대학교 논문은 저작권에 의해 보호받습니다. | - |
| dc.title | Biological and Molecular Characteristics of Senescent Melanocytes | - |
| dc.type | Thesis | - |
| dc.contributor.affiliation | 아주대학교 일반대학원 | - |
| dc.contributor.department | 일반대학원 의학과 | - |
| dc.date.awarded | 2022. 8 | - |
| dc.description.degree | Doctoral | - |
| dc.identifier.localId | 1254126 | - |
| dc.identifier.uci | I804:41038-000000032209 | - |
| dc.identifier.url | https://dcoll.ajou.ac.kr/dcollection/common/orgView/000000032209 | - |
| dc.subject.keyword | Autophagy | - |
| dc.subject.keyword | Melanosome transport | - |
| dc.subject.keyword | Senescent melanocytes | - |
| dc.description.alternativeAbstract | Background: Senescent melanocytes accumulate with age and may have a role in the aging process. Objective: To investigate the biological and molecular characteristics of senescent melanocytes. Materials and methods: Two in vitro senescence models of melanocytes, replicative and ultraviolet B (UVB)-induced models, were developed. The molecules involved in melanogenesis, melanosome transporting machinery and autophagic activities were examined. Results: Senescent melanocytes were confirmed with the increased expression of p16INK4a and the accumulation of Senescence Associated β-Galactosidase (SA-β-Gal). The total melanin content was increased in senescent melanocytes. However, it was not correlated with tyrosinase activity and microphthalmia-associated transcription factor (MITF) levels. Expression of melanosome transporting machinery, such as ras-related protein Rab-27A, melanophilin and myosin-Va, was decreased in senescent melanocytes, suggesting a defect in melanosome transport. Those senescent cells showed reduced autophagic activities. Microtubule-associated protein 1 light chain 3 (LC3)-II, which is a component of autophagosomes, was down-regulated. The levels of Beclin 1 and autophagy related 5 (ATG5) were also decreased. Conclusion: Senescent melanocytes are characterized by melanin retention which is associated with melanosome transport defects and autophagy impairment. | - |
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