PGA2-induced HO-1 attenuates G2M arrest by modulating GADD45α expression
PGA2-induced HO-1 attenuates G2M arrest by modulating GADD45α expression
Yun-Jeong Choe(Department of Biochemistry, College of Medicine, The Catholic University of Korea, Korea); 고경원(Department of Biochemistry, College of Medicine, The Catholic University of Korea, Korea); Hyein Lee(Department of Biochemistry, College of Medicine, The Catholic University of Korea, Korea); 이선영(Department of Biochemistry, College of Medicine, The Catholic University of Korea, Korea); Byung-Chul Kim(Department of Biochemistry, College of Natural Sciences, Kangwon National University, Korea); Ho-Shik Kim(Department of Biochemistry, College of Medicine, The Catholic University of Korea, Korea); Ho-Shik Kim(Department of Biochemistry, College of Medicine, The Catholic University of Korea, Korea)
11권 4호, 465~474쪽
초록
Prostaglandin (PG) A2, a cyclopentenone PG, arrested the growth of U2OS cells in the G2M phase. While inducing G2M arrest, PGA2 increased the expression of heme oxygenase-1 (HO-1) at the level of transcription along with the accumulation of ROS and the activation of MAPKs including JNK, p38MAPK, and ERK1/2. Among the MAPKs, the inhibition of p38MAPK by a specific chemical inhibitor SB203580, or by RNA interference, but not JNK or ERK1/2, attenuated the PGA2-induced transcription of HO-1. Nacetylcysteine (NAC), a ROS scavenger, prevented PGA2-induced G2M arrest, p38MAPK activation and transcriptional induction of HO-1. PGA2 also stimulated GADD45α expression at the level of transcription, and the knockdown of GADD45α repressed PGA2- induced G2M arrest. Finally, the knockdown of the HO-1 protein elevated PGA2-induced GADD45α expression as well as G2M arrest. Collectively, these results suggest that PGA2 causes an increase in ROS accumulation which initiates both HO-1 transcription via p38MAPK, and G2M arrest via GADD45α transcription, and HO-1 attenuates G2M arrest by modulating the expression of GADD45α.
Abstract
Prostaglandin (PG) A2, a cyclopentenone PG, arrested the growth of U2OS cells in the G2M phase. While inducing G2M arrest, PGA2 increased the expression of heme oxygenase-1 (HO-1) at the level of transcription along with the accumulation of ROS and the activation of MAPKs including JNK, p38MAPK, and ERK1/2. Among the MAPKs, the inhibition of p38MAPK by a specific chemical inhibitor SB203580, or by RNA interference, but not JNK or ERK1/2, attenuated the PGA2-induced transcription of HO-1. Nacetylcysteine (NAC), a ROS scavenger, prevented PGA2-induced G2M arrest, p38MAPK activation and transcriptional induction of HO-1. PGA2 also stimulated GADD45α expression at the level of transcription, and the knockdown of GADD45α repressed PGA2- induced G2M arrest. Finally, the knockdown of the HO-1 protein elevated PGA2-induced GADD45α expression as well as G2M arrest. Collectively, these results suggest that PGA2 causes an increase in ROS accumulation which initiates both HO-1 transcription via p38MAPK, and G2M arrest via GADD45α transcription, and HO-1 attenuates G2M arrest by modulating the expression of GADD45α.
- 발행기관:
- 대한독성 유전단백체 학회
- 분류:
- 분자유전