Clinical and Experimental Pediatrics

대한소아청소년과학회 (The Korean Pediatric Society)
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신경세포 분화에서 세포주기 조절인자로서의 NELL2 유전자의 역할

NELL2 gene as regulator of cell cycle in neuron differentiation

  • 정미림 (울산대학교 의과대학 소아과학교실) ;
  • 오연미 (울산대학교 의과대학 소아과학교실) ;
  • 박우생 (울산대학교 의과대학 소아과학교실) ;
  • 박상규 (울산대학교 의과대학 소아과학교실)
  • Joung, Mi Rim (Department of Pediatrics, College of Medicine, Ulsan University Hospital) ;
  • Oh, Yeon Mi (Department of Pediatrics, College of Medicine, Ulsan University Hospital) ;
  • Park, Woo Saeng (Department of Pediatrics, College of Medicine, Ulsan University Hospital) ;
  • Park, Sang Kyu (Department of Pediatrics, College of Medicine, Ulsan University Hospital)
  • 투고 : 2006.07.21
  • 심사 : 2006.08.30
  • 발행 : 2006.10.15
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초록

목 적 : 신경세포 분화에 있어 NELL2가 세포 주기와 세포자 멸사에 어떤 영향을 미치는지를 규명하고자 하였다. 방 법 : HiB5 세포에 NELL2를 전달감염시켜 배양하여 세포수를 측정하였다. 세포자멸사를 분석하기 위해 DNA 분절검사를 시행하였으며 PI염색으로 DNA양을 측정하였다. 세포주기의 조절에 관여하는 단백질에 대한 NELL2의 효과를 측정하기 위하여 Western blot과 면역염색을 시행하였다. 결 과 : NELL2를 전달감염시킨 군에서 세포수가 의미가 있게 적었고 DNA 분절검사에서 세포자멸사를 확인하였으며 $G_1$ 정지가 증가하였다. Western blot과 면역염색결과 Rb단백, p53, E2F1(KH-95)이 NELL2를 전달감염시킨 군에서 증가하고 cyclin D가 NELL2를 전달감염시킨 군에서 감소하였다. 결 론 : HiB5 세포에서 NELL2에 의하여 일정 수준에서의 세포자멸사가 동반되고 세포 주기에 있어 $G_1$기의 정지가 일어나며 세포주기를 조절하는 단백질의 변화가 발생함을 확인하였다. 따라서 NELL2가 뇌에서 신경세포 분화에 중요한 역할을 할 걸로 생각된다.

Purpose : Because NELL2 expression is strictly restricted only in neurons in developing and post-differentiated neural tissues, it is thought to be involved in the neuronal differentiation during development and in the maintenance of neuronal physiology in the post-differentiated neurons. In this study, we examined whether NELL2 is involved in the regulation of cell cycle and apoptosis in the hippocampal neuroprogenitor HiB5 cells. Methods : Effects of NELL2 on the cultured HiB5 cell numbers, DNA fragmentation, and proteins involved in the regulation of the cell cycle were measured. Results : NELL2 induced a decrease in cell numbers and an increase in G1 phase arrest. Moreover, transfection of NELL2 resulted in an increase of DNA fragmentation that shows an evidence of apoptosis. Contents of proteins involved in the regulation of cell cycle were also changed by transfection of NELL2 expression vectors. Conclusion : This study suggests that NELL2 plays an important role in the regulation of cell cycle and apoptosis of neurons.

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