Genetic Catalytic Inactivation of GRK5 Impairs Cardiac Function in Mice Via Dysregulated P53 Levels.
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ABSTRACT:
SUBMITTER: Marzano F
PROVIDER: S-EPMC9079799 | biostudies-literature | 2022 Apr
REPOSITORIES: biostudies-literature
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Genetic Catalytic Inactivation of GRK5 Impairs Cardiac Function in Mice Via Dysregulated P53 Levels.
Marzano Federica F Liccardo Daniela D Elia Andrea A Mucio Ines I de Lucia Claudio C Lucchese Anna Maria AM Gao Erhe E Ferrara Nicola N Rapacciuolo Antonio A Paolocci Nazareno N Rengo Giuseppe G Koch Walter J WJ Cannavo Alessandro A
JACC. Basic to translational science 20220309 4
GRK5's catalytic activity in regulating basal and stressed cardiac function has not been studied. Herein, we studied knock-in mice in which GRK5 was mutated to render it catalytically inactive (K215R). At baseline, GRK5-K215R mice showed a marked decline in cardiac function with increased apoptosis and fibrosis. In vitro, restriction of GRK5 inside the nucleus of cardiomyocytes resulted in enhanced cell death along with higher p53 levels. Moreover, in fibroblasts, we demonstrated that K215R muta ...[more]
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