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Artículo

Dystrophin proteolysis: a potential target for MMP-2 and its prevention by ischemic preconditioning

Buchholz, BrunoIcon ; Perez, Virginia; Siachoque Montaño, Nadezda Ann Alexandra; Miksztowicz, Verónica JulietaIcon ; Berg, Gabriela AliciaIcon ; Rodríguez, Manuel; Donato, Pablo MartínIcon ; Gelpi, Ricardo JorgeIcon
Fecha de publicación: 07/2014
Editorial: American Physiological Society
Revista: American Journal of Physiology - Heart and Circulatory Physiology
ISSN: 0363-6135
Idioma: Inglés
Tipo de recurso: Artículo publicado
Clasificación temática:
Otras Medicina Básica

Resumen

Dystrophin is responsible for the mechanical stabilization of the sarcolemma, and it has been shown that it is one of the most sensitive proteins to ischemic injury. However, the enzyme responsible for this proteolysis is still unknown. Isolated rabbit hearts were subjected to 30 min of global ischemia with and without reperfusion (180 min) to determine whether dystrophin is cleaved by matrix metalloproteinase (MMP)-2 during acute ischemia and whether ischemic preconditioning (PC) prevents dystrophin breakdown through MMP-2 inhibition. The activity of MMP-2 was evaluated by zymography and using doxycycline as an inhibitor. Also, to stimulate MMP-2 activity without ischemia, SIN-1 was administered in the absence and presence of doxycycline. Finally, we considered the PC effect on MMP-2 activity and dystrophin expression. The dystrophin level decreased during ischemia, reaching 21% of control values (P 0.05), but the spectrin level remained unchanged. MMP-2 activity increased 71% during ischemia compared with control values (P 0.05). Doxycycline administration before ischemia prevented dystrophin breakdown. In normoxic hearts, SIN-1 increased thiobarbituric acid-reactive substances by 33% (P 0.05) and MMP-2 activity by 36% (P 0.05) and significantly reduced the dystrophin level to 23% of control values (P 0.05). PC significantly prevented dystrophin breakdown by inhibiting MMP-2 activity, and the dystrophin level reached 89% of control values (P 0.05). In conclusion, MMP-2 could be responsible for the proteolysis of dystrophin. Thus, dystrophin emerges as a possible novel substrate for MMP-2 in the context of ischemic injury. Furthermore, our results demonstrate that ischemic PC prevents dystrophin breakdown most likely by inhibiting MMP-2 activity.
Palabras clave: Myocardial Infarction , Dystrophin , Matrix Metalloproteinase 2
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info:eu-repo/semantics/openAccess Excepto donde se diga explícitamente, este item se publica bajo la siguiente descripción: Creative Commons Attribution-NonCommercial-ShareAlike 2.5 Unported (CC BY-NC-SA 2.5)
Identificadores
URI: http://hdl.handle.net/11336/30743
DOI: http://dx.doi.org/10.1152/ajpheart.00242.2013
URL: http://www.physiology.org/doi/abs/10.1152/ajpheart.00184.2014
Colecciones
Articulos(IBIMOL)
Articulos de INSTITUTO DE BIOQUIMICA Y MEDICINA MOLECULAR
Articulos(OCA HOUSSAY)
Articulos de OFICINA DE COORDINACION ADMINISTRATIVA HOUSSAY
Citación
Buchholz, Bruno; Perez, Virginia; Siachoque Montaño, Nadezda Ann Alexandra; Miksztowicz, Verónica Julieta; Berg, Gabriela Alicia; et al.; Dystrophin proteolysis: a potential target for MMP-2 and its prevention by ischemic preconditioning; American Physiological Society; American Journal of Physiology - Heart and Circulatory Physiology; 307; 1; 7-2014; 88-96
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