Role of DJ-1 in Modulating Glycative Stress in Heart Failure.
J Am Heart Assoc
; 9(4): e014691, 2020 02 18.
Article
en En
| MEDLINE
| ID: mdl-32067589
ABSTRACT
Background DJ-1 is a ubiquitously expressed protein typically associated with the development of early onset Parkinson disease. Recent data suggest that it also plays a role in the cellular response to stress. Here, we sought to determine the role DJ-1 plays in the development of heart failure. Methods and Results Initial studies found that DJ-1 deficient mice (DJ-1 knockout; male; 8-10 weeks of age) exhibited more severe left ventricular cavity dilatation, cardiac dysfunction, hypertrophy, and fibrosis in the setting of ischemia-reperfusion-induced heart failure when compared with wild-type littermates. In contrast, the overexpression of the active form of DJ-1 using a viral vector approach resulted in significant improvements in the severity of heart failure when compared with mice treated with a control virus. Subsequent studies aimed at evaluating the underlying protective mechanisms found that cardiac DJ-1 reduces the accumulation of advanced glycation end products and activation of the receptor for advanced glycation end products-thus, reducing glycative stress. Conclusions These results indicate that DJ-1 is an endogenous cytoprotective protein that protects against the development of ischemia-reperfusion-induced heart failure by reducing glycative stress. Our findings also demonstrate the feasibility of using a gene therapy approach to deliver the active form of DJ-1 to the heart as a therapeutic strategy to protect against the consequences of ischemic injury, which is a major cause of death in western populations.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Estrés Oxidativo
/
Proteína Desglicasa DJ-1
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Insuficiencia Cardíaca
Tipo de estudio:
Prognostic_studies
Límite:
Animals
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Humans
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Male
Idioma:
En
Revista:
J Am Heart Assoc
Año:
2020
Tipo del documento:
Article