2012 Fiscal Year Final Research Report
Oxidative stress during fetal-neonatal transition and the formation of a positive-feedback loop for the terminal differentiation of mammalian cardiomyocytes.
| Project/Area Number |
22300148
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Biomedical engineering/Biological material science
|
|---|
| Research Institution | Hokkaido University |
|---|
Principal Investigator |
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
SAITOH Tadashi 山形大学, 大学院・理工学研究科, 助教 (20454770)
|
|---|
| Project Period (FY) |
2010 – 2012
|
| Keywords | 心筋細胞 / 細胞周期 / 酸化ストレス / 正帰還ループ / 増殖能喪失 |
|---|
| Research Abstract |
Shortly after birth, mammalian cardiomyocytes irreversibly exit from the cell cycle and become terminally differentiated. The genetic cues for the irreversible exit from the cell cycle in mammalian cardiomyocytes 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 connexin43 (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. 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.
|
Research Products
(14 results)
