Inhibiting MARSs reduces hyperhomocysteinemia-associated neural tube and congenital heart defects

ABSTRACT: Hyperhomocysteinemia is a common metabolic disorder that imposes major adverse health consequences. Reducing homocysteine levels, however, is not always effective against hyperhomocysteinemia-associated pathologies. Herein, we report the potential roles of methionyl-tRNA synthetase (MARS)-generated homocysteine signals in neural tube defects (NTDs) and congenital heart defects (CHDs). Increased copy numbers of MARS and/or MARS2 were detected in NTD and CHD patients. MARSs sense homocysteine and transmit its signal by inducing protein lysine (N)-homocysteinylation. Here we identified hundreds of novel N-homocysteinylated proteins. N-homocysteinylation of superoxide dismutases provided new mechanistic insights for homocysteine-induced oxidative stress, apoptosis, and Wnt-signalling deregulat

SUBMITTER: Xinyu Mei 

PROVIDER: S-SCDT-EMM-2018-09469-T | biostudies-other |

REPOSITORIES: biostudies-other