생명과학회지 (Journal of Life Science)

  • 제23권1호
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  • Pages.131-136
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  • 2013
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  • 1225-9918(pISSN)
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  • 2287-3406(eISSN)
한국생명과학회 (Korean Society of Life Science)
권호 표지
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인간 제대혈 유래 혈관내피세포의 혈관 튜브 형성능에 미치는 Sirtuin-2 (SIRT2)의 역활

The Role of Sirtuin-2 in Tubular Forming Activity of Human Umbilical Vein Endothelial Cells

  • 정석윤 (부산대학교 의학전문대학원 생리학교실 혈관의학 및 줄기세포학 실험실) ;
  • 김철민 (부산대학교 의학전문대학원 생리학교실 혈관의학 및 줄기세포학 실험실) ;
  • 김다연 (부산대학교 의학전문대학원 생리학교실 혈관의학 및 줄기세포학 실험실) ;
  • 이동형 (부산대학교병원 산부인과) ;
  • 이규섭 (부산대학교병원 산부인과) ;
  • 권상모 (부산대학교 의학전문대학원 생리학교실 혈관의학 및 줄기세포학 실험실)
  • Jung, Seok Yun (Laboratory of Vascular Medicine & Stem Cell Biology, Department of Physiology, School of Medicine, Pusan National University) ;
  • Kim, Chul Min (Laboratory of Vascular Medicine & Stem Cell Biology, Department of Physiology, School of Medicine, Pusan National University) ;
  • Kim, Da Yeon (Laboratory of Vascular Medicine & Stem Cell Biology, Department of Physiology, School of Medicine, Pusan National University) ;
  • Lee, Dong Hyung (Department of Obstetrics & Gynecology, College of Medicine, Pusan National University) ;
  • Lee, Kyu Sup (Department of Obstetrics & Gynecology, College of Medicine, Pusan National University) ;
  • Kwon, Sang-Mo (Laboratory of Vascular Medicine & Stem Cell Biology, Department of Physiology, School of Medicine, Pusan National University)
  • 투고 : 2012.10.15
  • 심사 : 2013.01.06
  • 발행 : 2013.01.30
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초록

Sirtuin family 단백질은 암, 당뇨, 심혈관 질환, 뇌신경계 질환과 같은 노화와 연관된 질병들의 발병에 중요한 역할을 하는 것으로 알려져 있다. 우선적으로 혈관내피세포를 이용하여 Hypoxia에서의 sirtuin family의 발현을 확인한 결과, SIRT2 mRNA가 가장 강하게 발현되는 결과를 얻었다. 혈관신생과정에서의 SIRT2 단백질의 생리학적 역할을 규명하고자, 본 실험실에서는 저산소상태에서의 SIRT2의 생리학적인 의미에 주안점을 두었다. Normoxia에서 SIRT2는 세포질에 존재하고 있으나, hypoxia에 의해서 SIRT2 단백질이 핵 내로 이동이 일어남을 확인하였다. 또한 hypoxia에 의해서 SIRT2와 혈관신생인자인 VEGF의 발현이 증가하며, Normoxia와 hypoxia 두 환경에서 혈관내피세포의 혈관형성능력이 SIRT2 inhibitor인 AK-1에 의해서 억제된 것을 확인하였다. 본 연구결과를 통해서 SIRT2가 혈관신생과정을 조절하는 중요한 역할을 함을 시사하였다.

Sirtuin proteins have emerged as important modulators of several age-associated diseases. These include cancer and diabetes, as well as cardiovascular and neurodegenerative diseases. Among the sirtuin family members, SIRT2 mRNA is strongly expressed. To investigate the pathophysiological significance of SIRT2 as a primary regulator of angiogenesis, we focused on the biological role of SIRT2 under hypoxic conditions, examining the gene expression pattern of sirtuin family members in human umbilical vein endothelial cells (HUVECs). SIRT2 was expressed primarily in the cytoplasm, but it was dynamically trans-localized in the nuclear by hypoxia stimuli. Interestingly, both SIRT2 and the pro-angiogenic factor, VEGF, were up- regulated by hypoxia. A Matrigel assay demonstrated that the HUVECs formed a tube-like structure under hypoxia. The SIRT2 inhibitor, AK-1, significantly decreased the tube-forming activity of the HUVECs under either normoxia or hypoxia conditions. These findings suggest that SIRT2 might be a key regulator of angiogenesis.

키워드

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