Targeting N-Myristoylation Through NMT2 Prevents Cardiac Hypertrophy and Heart Failure.
JACC Basic Transl Sci
; 8(10): 1263-1282, 2023 Oct.
Article
em En
| MEDLINE
| ID: mdl-38094695
ABSTRACT
Protein diversity can increase via N-myristoylation, adding myristic acid to an N-terminal glycine residue. In a murine model of pressure overload, knockdown of cardiac N-myristoyltransferase 2 (NMT2) by adeno-associated virus 9 exacerbated cardiac dysfunction, remodeling, and failure. Click chemistry-based quantitative chemical proteomics identified substrate proteins of N-myristoylation in cardiac myocytes. N-myristoylation of MARCKS regulated angiotensin II-induced cardiac pathological hypertrophy by preventing activations of Ca2+/calmodulin-dependent protein kinase II and histone deacetylase 4 and histone acetylation. Gene transfer of NMT2 to the heart reduced cardiac dysfunction and failure, suggesting targeting N-myristoylation through NMT2 could be a potential therapeutic approach for preventing cardiac remodeling and heart failure.
Texto completo:
1
Base de dados:
MEDLINE
Idioma:
En
Revista:
JACC Basic Transl Sci
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Japão