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Hokkaido University Collection of Scholarly and Academic Papers >
Graduate School of Information Science and Technology / Faculty of Information Science and Technology >
Peer-reviewed Journal Articles, etc >
Oxidative stress-induced formation of a positive-feedback loop for the sustained activation of p38 MAPK leading to the loss of cell division in cardiomyocytes soon after birth
| Title: | Oxidative stress-induced formation of a positive-feedback loop for the sustained activation of p38 MAPK leading to the loss of cell division in cardiomyocytes soon after birth |
| Authors: | Matsuyama, Daisuke Browse this author | | Kawahara, Koichi Browse this author →KAKEN DB |
| Keywords: | Perinatal oxidative stress | | Reactive oxygen species | | Connexin 43 | | Positive-feedback loop | | Binucleation | | P38 MAPK |
| Issue Date: | Sep-2011 |
| Publisher: | Springer Berlin / Heidelberg |
| Journal Title: | Basic Research in Cardiology |
| Volume: | 106 |
| Issue: | 5 |
| Start Page: | 815 |
| End Page: | 828 |
| Publisher DOI: | 10.1007/s00395-011-0178-8 |
| PMID: | 21479589 |
| Abstract: | Shortly after birth, mammalian cardiomyocytes irreversibly exit from the cell cycle and become terminally differentiated. The cellular mechanisms responsible for the cessation of cell division and terminal differentiation of cardiomyocytes soon after birth have intrigued developmental biologists as well as cardiovascular physicians, but the genetic cues for the irreversible exit from the cell cycle soon after birth remain largely unknown. We examined whether and if so how oxidative stress to mammalian hearts during fetal-neonatal transition produces changes in the proliferative activity and terminal differentiation of cardiomyocytes. Scavenging of reactive oxygen species (ROS) during fetal-neonatal transition, especially after birth, resulted in an increase in the proliferative activity and a decrease in the ratio of binucleated cardiomyocytes. Exposure to ROS in cultured cardiomyocytes increased the activity of p38 MAPK and the expression of connexin 43 (Cx43). Not only knockdown of Cx43 using siRNA but also the inhibition of p38 MAPK activity resulted in a significant decrease in the production of ROS in cardiomyocytes, suggesting that the signaling pathway ROS-p38 MAPK-Cx43 (especially, Cx43 at mitochondria, mtCx43) constituted a closed regulatory system with positive-feedback. In addition, continuous scavenging of ROS or suppression of p38 MAPK activity for 4 days after birth resulted in a significant decrease in the expression of mtCx43 and in the number of binucleated cardiomyocytes. This study demonstrated that the ROS-induced formation of a positive-feedback loop ROS-p38 MAPK-mtCx43 for the sustained activation of p38 MAPK soon after birth possibly contributes to the loss of cell division and binucleation in mammalian cardiomyocytes. |
| Rights: | The original publication is available at www.springerlink.com |
| Type: | article (author version) |
| URI: | http://hdl.handle.net/2115/49922 |
| Appears in Collections: | 情報科学院・情報科学研究院 (Graduate School of Information Science and Technology / Faculty of Information Science and Technology) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 河原 剛一
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