Human liver ischemia/reperfusion injury (IRI) is a common and major clinical problem complicating liver surgery and transplantation. The pathogenesis underlying IRI is complex, involving a series of signaling mediators and mechanisms. This study aimed to investigate the effects of Magnesium Isoglycyrrhizinate (MgIG) on the changes of oxidant stress and apoptosis induced by IRI in human hepatic ...

Nazarewicz RR, Dikalova AE, Bikineyeva A, Dikalov SI. Nox2 as a potential target of mitochondrial superoxide and its role in endothelial oxidative stress. Am J Physiol Heart Circ Physiol 305: H1131–H1140, 2013. First published August 16, 2013; doi:10.1152/ajpheart.00063.2013.—Superoxide (O2 ) production by the NADPH oxidases is implicated in the pathogenesis of many cardiovascular diseases, inc...

BACKGROUND Ischemic preconditioning accelerates suppression of gap junction (GJ) permeability during myocardial ischemia, and GJ blockers reduce infarct size. We hypothesized that the mitochondrial ATP-sensitive K+ (mitoKATP) channel is one of the mechanisms regulating GJ permeability through the mitogen-activated protein kinase ERK, leading to cardioprotection. METHODS AND RESULTS In isolate...

BACKGROUND Levosimendan protects rat liver against peroxidative injuries through mechanisms related to nitric oxide (NO) production and mitochondrial ATP-dependent K (mitoKATP) channels opening. However, whether levosimendan could modulate the cross-talk between apoptosis and autophagy in the liver is still a matter of debate. Thus, the aim of this study was to examine the role of levosimendan ...

Ischemic preconditioning, a phenomenon in which brief episodes of ischemia and reperfusion paradoxically protect the heart against subsequent lethal ischemia,1 has been conceptually divided into triggers and mediators/effectors.2,3 The trigger, which acts before the index ischemia, is followed by the protection of mediators/effectors during the lethal ischemia. Known triggers include activation...

Intracellular Mg²⁺ concentration ([Mg²⁺]i) and NO regulate cell survival and death. To reveal the involvement of NO in intracellular Mg²⁺ regulation, we visualized intracellular Mg²⁺ using the fluorescent Mg²⁺ indicator KMG-104-AM in rat hippocampal neurons. Pharmacological experiments using SNAP, 8-Br-cGMP, diazoxide and several inhibitors revealed that the NO/cGMP/Protein kinsase G (PKG) sign...

Background—The mitochondrial KATP channel (mitoKATP) has been implicated as an end effector or trigger of ischemic preconditioning (IP). Although a mitoKATP opener, diazoxide, mimics IP, mechanisms for the cardioprotective action remain unclear. Methods and Results—We measured Ca transients (CaTs) and mitochondrial inner membrane potential ( m) with confocal microscopy and the fluorescent probe...

INTRODUCTION Ischemia/Reperfusion (IR) injury mainly causes the increase of enzymes involved in myocytes injury including CK-MB (creatine kinase-MB) isoenzyme and LDH (lactate dehydrogenase). Leakage of CK-MB isoenzyme and LDH from myocardial tissues to blood is indicator of acute myocardial infarction. The aim of this study was to assess the effect of HEMADO on IR injury and its relationship w...

Ischemia postconditioning (IPo) is a promising strategy in reducing myocardial ischemia reperfusion (I/R) injury (MIRI), but its specific molecular mechanism is incompletely understood. Langendorff-perfused isolated rat hearts were subjected to global I/R and received IPo in the absence or presence of the mitochondrial ATP-sensitive potassium channel (mitoKATP) blocker 5-hydroxydecanoate (5-HD)...

Mitochondrial-initiated events protect the neurovascular unit against lethal stress via a process called preconditioning, which independently promotes changes in cerebrovascular tone through shared signaling pathways. Activation of adenosine triphosphate (ATP)-dependent potassium channels on the inner mitochondrial membrane (mitoKATP channels) is a specific and dependable way to induce protecti...