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KMID : 1034820150110040465
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Molecular & Cellular Toxicology
2015 Volume.11 No. 4 p.465 ~ p.474
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PGA2-induced HO-1 attenuates G2M arrest by modulating GADD45α expression
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Choe Yun-Jeong
Ko Kyoung-Won
Lee Hye-In
Lee Sun-Young
Kim Byung-Chul
Kim Ho-Shik
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Abstract
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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. N-acetylcysteine (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.
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KEYWORD
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Prostaglandin A2, Heme oxygenase-1, p38MAPK, GADD45α, G2M arrest, ROS
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