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Biological and Molecular Characteristics of Senescent Melanocytes
- Author(s)
- 이진욱
- Advisor
- 강희영
- Department
- 일반대학원 의학과
- Publisher
- The Graduate School, Ajou University
- Publication Year
- 2022-08
- Language
- eng
- 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.
- Alternative Abstract
- 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.
- Fulltext
- Appears in Collections:
- Graduate School of Ajou University > Department of Medicine > 4. Theses(Ph.D)
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