Journal of Life Science (생명과학회지)

Korean Society of Life Science (한국생명과학회)
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Prostaglandin A2-induced Apoptosis is Not Inhibited by Heme Oygenase-1 in U2OS Cells

U2OS 세포에서 prostaglandin A2에 의한 apoptosis는 heme oxygenase-1에 의하여 저해되지 않는다

  • Ko, Kyoung-Won (Department of Biochemistry, College of Medicine, The Catholic University of Korea) ;
  • Lee, Sun-Young (Department of Biochemistry, College of Medicine, The Catholic University of Korea) ;
  • Ahn, Ji-Hyun (Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, Chung-Ang University) ;
  • Kim, Jae-Taek (Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, Chung-Ang University) ;
  • Kim, In-Kyung (Department of Biochemistry, College of Medicine, The Catholic University of Korea) ;
  • Kim, Ho-Shik (Department of Biochemistry, College of Medicine, The Catholic University of Korea)
  • 고경원 (가톨릭대학교 의과대학 생화학교실) ;
  • 이선영 (가톨릭대학교 의과대학 생화학교실) ;
  • 안지현 (중앙대학교 의과대학 내과학교실) ;
  • 김재택 (중앙대학교 의과대학 내과학교실) ;
  • 김인경 (가톨릭대학교 의과대학 생화학교실) ;
  • 김호식 (가톨릭대학교 의과대학 생화학교실)
  • Published : 2008.11.30
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Abstract

Prostaglandin $A_2$ ($PGA_2$), one of cyclopentenone PGs, induced both apoptosis and heme oxygenase (HO)-1 expression in U2OS cells. $PGA_2$-induced apoptosis was not perturbed by either over-expression or knock-down of HO-1, whereas $H_2O_2$-induced cell death was inversely modulated by the expression level of HO-1. In addition, N-acetyl-L-cysteine (NAC), a thiol antioxidant, blocked both apoptosis and HO-1 expression induced by $PGA_2$. But, non-thiol antioxidants like butylated hydorxyanisole (BHA) and ascorbic acid did not block either apoptosis or HO-1-induction. Taken together, these results suggest that $PGA_2$ induces both apoptosis and HO-1 expression, which are critically related to the thiol- reactivity of $PGA_2$, but not oxidative stress, and HO-1 expression may be independent or functionally located downstream of apoptosis by $PGA_2$ without contribution to apoptosis progression.

Prostaglandin $A_2$ ($PGA_2$)는 사람 골육종 세포인 U2OS 세포주에서 apoptosis와 heme oxygenase (HO)-1의 발현을 함께 유도하였다. $PGA_2$에 의한 apoptosis는 HO-1의 과도한 발현이나 HO-1에 대한 small interfering RNA에 의한 발현저하에 의하여 변동되지 않았으나 $H_2O_2$에 의한 세포사망은 HO-1의 발현 수준에 반비례하여 변동되었다. 또한 thiol antioxidant인 N-acetyl-L-cysteine (NAC)은 $PGA_2$에 의한 세포사망과 HO-1의 발현 증가를 모두 차단하였지만, non-thiol antioxidant인 butylated hydroxyanisole (BHA)과 ascorbic acid는 세포사망과 HO-1의 발현 유도를 차단하지 않았다. 이와 같은 결과들은 $PGA_2$는 산화성 손상에 의해서가 아니라 $PGA_2$의 thiol-reactivity에 의하여 apoptosis와 HO-1의 발현을 유도하며, HO-1의 발현은 $PGA_2$에 의한 apoptosis와는 독립적인 현상이거나 기능적으로 apoptosis 유도의 하부에 위치하고 apoptosis의 진행에는 기여하지 않을 것이라는 것을 시사해 준다.

Keywords

References

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