Tan, Lin and Bogush, Nikolay and Naib, Hussain and Perry, Jennifer and Calvert, John W. and Martin, David I. K. and Graham, Robert M. and Naqvi, Nawazish and Husain, Ahsan (2019) Redox activation of JNK2α2 mediates thyroid hormone-stimulated proliferation of neonatal murine cardiomyocytes. Scientific Reports, 9 (1). ISSN 2045-2322
Full text not available from this repository.Abstract
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-2α2 (JNK2α2). JNK2α2, 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.
| Item Type: | Article |
|---|---|
| Subjects: | R Medicine > R Medicine (General) |
| Depositing User: | Repository Administrator |
| Date Deposited: | 09 Dec 2019 02:54 |
| Last Modified: | 09 Dec 2019 02:54 |
| URI: | https://eprints.victorchang.edu.au/id/eprint/899 |
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