TBC1 domain family member 25 protects against myocardial apoptosis and the proinflammatory response triggered by ischemia-reperfusion injury through suppression of the TAK1-JNK/p38 MAPK signaling cascade.
In Vitro Cell Dev Biol Anim
; 59(10): 796-810, 2023 Dec.
Article
en En
| MEDLINE
| ID: mdl-38100060
ABSTRACT
TBC1 domain family member 25 (TBC1D25) is a crucial mediator of signal transduction involved in the development of several diseases. Particularly, a cardioprotective role of TBC1D25 has been raised due to its antagonistic action on cardiac hypertrophy. However, whether TBC1D25 protects the myocardium from ischemia-reperfusion injury has not been reported. This work aimed to determine the role of TBC1D25 in myocardial ischemia-reperfusion (MIR) injury and to explore the potential mechanisms involved. Marked decreases in TBC1D25 levels occurred in cardiomyocytes suffering hypoxia/reoxygenation (H/R) injury in vitro and myocardium tissues of rats with MIR injury in vivo. Cardiomyocytes overexpressing TBC1D25 were protected from apoptosis and inflammation triggered by H/R, whereas TBC1D25-deficient cardiomyocytes were more sensitive to H/R injury. Intramyocardial injection of recombinant adenovirus expressing TBC1D25 into rats reduced infarct size and cardiac injury triggered by MIR injury accompanied by decreased myocardial apoptosis and inflammation. A subsequent mechanistic investigation revealed that the signaling cascade of transforming growth factor-ß-activated kinase 1 (TAK1)-c-Jun N-terminal kinase (JNK)/p38 mitogen-activated protein kinase (MAPK) activated under H/R or MIR conditions was markedly restrained by TBC1D25 overexpression. Moreover, TAK1 blockade remarkably reversed the TBC1D25 deficiency-induced aggravating effect on H/R injury. The work concludes that TBC1D25 protects against MIR injury through action on the TAK1-JNK/p38 MAPK signaling cascade. This work suggests TBC1D25 as a potential therapeutic target for MIR injury.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Daño por Reperfusión Miocárdica
Límite:
Animals
Idioma:
En
Revista:
In Vitro Cell Dev Biol Anim
Asunto de la revista:
BIOLOGIA
Año:
2023
Tipo del documento:
Article
País de afiliación:
China