| First Author | Tan L | Year | 2019 |
| Journal | Sci Rep | Volume | 9 |
| Issue | 1 | Pages | 17731 |
| PubMed ID | 31776360 | Mgi Jnum | J:308094 |
| Mgi Id | MGI:6717920 | Doi | 10.1038/s41598-019-53705-1 |
| Citation | Tan L, et al. (2019) Redox activation of JNK2alpha2 mediates thyroid hormone-stimulated proliferation of neonatal murine cardiomyocytes. Sci Rep 9(1):17731 |
| abstractText | Mitochondria-generated reactive oxygen species (mROS) are frequently associated with DNA damage and cell cycle arrest, but physiological increases in mROS serve to regulate specific cell functions. T3 is a major regulator of mROS, including hydrogen peroxide (H2O2). Here we show that exogenous thyroid hormone (T3) administration increases cardiomyocyte numbers in neonatal murine hearts. The mechanism involves signaling by mitochondria-generated H2O2 (mH2O2) acting via the redox sensor, peroxiredoxin-1, a thiol peroxidase with high reactivity towards H2O2 that activates c-Jun N-terminal kinase-2alpha2 (JNK2alpha2). JNK2alpha2, a relatively rare member of the JNK family of mitogen-activated protein kinases (MAPK), phosphorylates c-Jun, a component of the activator protein 1 (AP-1) early response transcription factor, resulting in enhanced insulin-like growth factor 1 (IGF-1) expression and activation of proliferative ERK1/2 signaling. This non-canonical mechanism of MAPK activation couples T3 actions on mitochondria to cell cycle activation. Although T3 is regarded as a maturation factor for cardiomyocytes, these studies identify a novel redox pathway that is permissive for T3-mediated cardiomyocyte proliferation-this because of the expression of a pro-proliferative JNK isoform that results in growth factor elaboration and ERK1/2 cell cycle activation. |
