Redox activation of JNK2α2 mediates thyroid hormone-stimulated proliferation of neonatal murine cardiomyocytes
Year: 2019
Type: article
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.
Source: Scientific Reports
Authors: Lin Tan, Nikolay Bogush, Hussain Naib, Jennifer Perry, John W. Calvert, David I. K. Martin, Robert M. Graham, Nawazish Naqvi, Ahsan Husain
Institutions: Emory University, Victor Chang Cardiac Research Institute
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $1,790
Funders: U.S. Department of Health and Human Services, American Heart Association, Emory University, Stem Cells Australia, Fondation Leducq, National Institutes of Health, Medical Research Council, Australian Research Council, National Health and Medical Research Council, National Heart, Lung, and Blood Institute
Awards: Hydrogen sulfide attenuates heart failure through Nrf2-mediated signaling, G1994527326, Molecular mechanisms and therapeutic approaches to cardiac development, regeneration and disease, Research Training in Academic Cardiology, G403685880, Nitrite Mediated Cardioprotection, G4846968251, Preclinical Consortium to Facilitate Translation of Cardioprotective Therapies, Stem Cells Australia, Functional Cardio-Metabolomics, Role of Chymase In The Post-Myocardial Infarction Heart, Identifying mechanism of T3 mediated proliferation in mitotically quiescent cardiomyocytes, G7594474092, Cardioprotective Actions of Hydrogen Sulfide, Development of the Postnatal Heart, G9000125557, G9000250830
OpenAlex ID: W2991018114