Specific inhibition of the mitochondrial permeability transition prevents lethal reperfusion injury

Argaud, Laurent; Gateau-Roesch, Odile; Muntean, Daniela-Lucia; Chalabreysse, Lara; Loufouat, Joseph; Robert, Dominique; Ovize, Michel

doi:10.1016/j.yjmcc.2004.12.001

Cited by 312 publications

(240 citation statements)

References 48 publications

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“…Interestingly, in this same study, delaying NIM811 administration by 12 h following injury was effective in preventing cytoskeletal degradation. Finally, NIM811 significantly reduced reperfusion injury following experimental acute myocardial infarction [94,96,99]. Collectively, the findings of these studies suggest that an approach that targets the mPTP can be generalized to several models of cell death.…”

Section: Targeting the Mptp In Acute Scimentioning

confidence: 75%

“…Numerous experimental studies and clinical observations have demonstrated that the immunosuppressant cyclosporin A (CsA), which inhibits mPT and promotes mitochondrial function, may be of therapeutic benefit in the treatment of acute traumatic brain injury (TBI), SCI, cerebral ischemia, and reperfusion injury following acute myocardial infarction [94][95][96][97][98][99][100][101][102][103]. Phase I clinical trials for the acute treatment of severe TBI have been performed, and follow-up trials have been proposed [104].…”

Section: Targeting the Mptp In Acute Scimentioning

confidence: 99%

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Targeting Mitochondrial Function for the Treatment of Acute Spinal Cord Injury

et al. 2011

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Summary: Traumatic injury to the mammalian spinal cord is a highly dynamic process characterized by a complex pattern of pervasive and destructive biochemical and pathophysiological events that limit the potential for functional recovery. Currently, there are no effective therapies for the treatment of spinal cord injury (SCI) and this is due, in part, to the widespread impact of the secondary injury cascades, including edema, ischemia, excitotoxicity, inflammation, oxidative damage, and activation of necrotic and apoptotic cell death signaling events. In addition, many of the signaling pathways associated with these cascades intersect and initiate other secondary injury events. Therefore, it can be argued that therapeutic strategies targeting a specific biochemical cascade may not provide the best approach for promoting functional recovery. A "systems approach" at the subcellular level may provide a better strategy for promoting cell survival and function and, as a consequence, improve functional outcomes following SCI. One such approach is to study the impact of SCI on the biology and function of mitochondria, which serve a major role in cellular bioenergetics, function, and survival. In this review, we will briefly describe the importance and unique properties of mitochondria in the spinal cord, and what is known about the response of mitochondria to SCI. We will also discuss a number of strategies with the potential to promote mitochondrial function following SCI.

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Section: Targeting the Mptp In Acute Scimentioning

confidence: 75%

Section: Targeting the Mptp In Acute Scimentioning

confidence: 99%

Targeting Mitochondrial Function for the Treatment of Acute Spinal Cord Injury

et al. 2011

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“…24 It has become increasing clear that prevention of mPTP opening plays a critical role as an end-effector in myocardial protection against ischemia-reperfusion injury. [25][26][27][28][29] Whether isoflurane inhibits mPTP by attenuating glycogen synthase kinase-3β activity through Erk1/2-p70s6K signaling is presently unknown. This hypothesis is being actively investigated by our laboratory, and certainly appears to be very plausible based on recent findings indicating that desflurane-induced preconditioning is mediated by inhibition of mitochondrial permeability transition.…”

Section: Discussionmentioning

confidence: 99%

Role of Erk1/2, p70s6K, and eNOS in isofluraneinduced cardioprotection during early reperfusionin vivo

Krolikowski

Weihrauch

Bienengraeber

et al. 2006

Can J Anesth/J Can Anesth

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Purpose: Administration of isoflurane during early reperfusion after prolonged coronary artery occlusion decreases myocardial infarct size by activating phosphatidylinositol-3-kinase (PI3K) signal transduction. The extracellular signal-related kinases (Erk1/2) represent a redundant mechanism by which signaling elements downstream from PI3K, including 70-kDA ribosomal protein s6 kinase (p70s6K) and endothelial nitric oxide synthase (eNOS), may be activated to reduce reperfusion injury. We tested the hypothesis Erk1/2, p70s6K, and eNOS mediate isoflurane-induced postconditioning in rabbit myocardium in vivo. Methods: Barbiturate-anesthetized rabbits (n = 78) instrumented for measurement of systemic hemodynamics were subjected to a 30-min coronary occlusion followed by three hours reperfusion. Rabbits were randomly assigned to receive 0.9% saline (control), the Erk1/2 inhibitor PD 098059 (2 mg·kg -1 ), the p70s6K inhibitor rapamycin (0.25 mg·kg -1 ), the nonselective nitric oxide synthase (NOS) inhibitor N-nitro-L-arginine methyl ester (L-NAME; 10 mg·kg -1 ), the selective inducible NOS antagonist aminoguanidine hydrochloride (AG, 300 mg·kg -1 ), or the selective neuronal NOS inhibitor 7-nitroindazole (7-NI, 50 mg·kg -1 ) in the presence or absence of 1.0 minimum alveolar concentration isoflurane administered for three minutes before and two minutes after reperfusion. Results: Brief exposure to 1.0 minimum alveolar concentration isoflurane reduced (P < 0.05) infarct size (21 ± 4% [mean ± SD] of left ventricle area at risk, respectively; triphenyltetrazolium staining) as compared to control (41 ± 5%). PD 098059, rapamycin, and L-NAME, but not AG nor 7-NI, abolished the protection produced by isoflurane. Conclusion:The results suggest that the protective effects of isoflurane against infarction during early reperfusion are mediated by Erk1/2, p70s6K, and eNOS in vivo. Objectif : L'administration d'isoflurane pendant la reperfusion pré-coce qui suit une occlusion prolongée de l'artère coronaire diminue la taille de l'infarctus myocardique en activant la transduction du signal de la phosphatidylinositol-3-kinase (PI3K). Les kinases extracellulaires reliées au signal (Erk1/2) représentent un mécanisme redondant par lequel le signalement des éléments en aval à partir de PI3K, incluant la s6 kinase de protéines ribosomales

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“…The opening of MPTP is favored by calcium overload due to ischemia, ATP depletion, accumulation of inorganic phosphate and burst production of ROS upon reperfusion (Kowaltowski et al, 2001;Weiss et al, 2003). Using pharmacological inhibitors such as cyclosporine A (CsA) and NIM811, inhibition of MPTP opening during the early reperfusion period has been shown to confer cardioprotection against myocardial ischemia-reperfusion injury (Argaud et al, 2005a). CsA, an immunosuppressive drug, has been shown to attenuate MPTP opening and improve mitochondrial respiratory function in cardiomyocytes isolated from failing hearts (Sharov et al, 2007).…”

Section: Introductionmentioning

confidence: 99%