Minocycline inhibits caspase activation and reactivation, increases the ratio of XIAP to smac/DIABLO, and reduces the mitochondrial leakage of cytochrome C and smac/DIABLO

105Citations
Citations of this article
30Readers
Mendeley users who have this article in their library.

Abstract

Objectives This study is aimed at investigating the novel use of minocycline for cardiac protection during ischemia/reperfusion (I/R) injury, as well as its mechanism of action. Background Minocycline is a tetracycline with anti-inflammatory properties, which is used clinically for the treatment of diseases such as urethritis and rheumatoid arthritis. Experimentally, minocycline has also been shown to be neuroprotective in animal models of cerebral ischemia and to delay progression and improve survival in mouse models of neurodegenerative diseases. Methods We studied 62 rat intact hearts exposed to I/R and cell cultures of neonatal and adult rat ventricular myocytes. Results Minocycline significantly reduced necrotic and apoptotic cell death, both in neonatal and adult myocytes, not only when given prior to hypoxia (p < 0.001), but also at reoxygenation (p < 0.05). Moreover, in the intact heart exposed to I/R, in vivo treatment with minocycline promoted hemodynamic recovery (p < 0.001) and cell survival, with reduction of infarct size (p < 0.001), cardiac release of creatine phosphokinase (p < 0.001), and apoptotic cell death (p < 0.001). In regard to its antiapoptotic mechanism of action, minocycline significantly reduced the expression level of initiator caspases, increased the ratio of XIAP to Smac/DIABLO at both the messenger RNA and protein level, and prevented mitochondrial release of cytochrome c and Smac/DIABLO (all, p < 0.05). These synergistic actions dramatically prevent the post-ischemic induction of caspase activity associated with cardiac I/R injury. Conclusions Because of its safety record and multiple novel mechanisms of action, minocycline may be a valuable cardioprotective agent to ameliorate cardiac dysfunction and cell loss associated with I/R injury. © 2004 by the American College of Cardiology Foundation.

Cite

CITATION STYLE

APA

Scarabelli, T. M., Stephanou, A., Pasini, E., Gitti, G., Townsend, P., Lawrence, K., … Gardin, J. (2004). Minocycline inhibits caspase activation and reactivation, increases the ratio of XIAP to smac/DIABLO, and reduces the mitochondrial leakage of cytochrome C and smac/DIABLO. Journal of the American College of Cardiology, 43(5), 865–874. https://doi.org/10.1016/j.jacc.2003.09.050

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free