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Germán A Colareda, Alicia E Consolini
OBJECTIVES: Low-flow ischemia (LFI) is consequent to coronary disease and produces cardiac stunning during reperfusion (R). Energetic performance and mechanisms of Ca2+ handling during LFI/R are not known. Moreover, cardioprotection of the phytoestrogen genistein (Gen) remains to be demonstrated in LFI/R. The aim was to study the mechanisms of the stunning consequent to LFI/R and the effects of Gen on both sexes. METHODS: Rat ventricles were perfused inside a calorimeter to measure maximal pressure development (P) and total heat rate (Ht) before and during exposition to LFI/R...
September 2018: Journal of Pharmacy and Pharmacology
Martin Stroethoff, Iris Christoph, Friederike Behmenburg, Annika Raupach, Sebastian Bunte, Semra Senpolat, André Heinen, Markus W Hollmann, Alexander Mathes, Ragnar Huhn
Activation of melatonin receptors induces cardioprotection. Mitochondrial potassium channels (mKCa and mKATP) are involved in the signaling cascade of preconditioning. The melatonin receptor agonist ramelteon is an approved oral medication for treatment of insomnia, but nothing is known about possible cardioprotective properties. We investigated whether (1) ramelteon induces cardioprotection mediated by the melatonin receptor; (2) this effect is concentration-dependent; and (3) mKCa and/or mKATP channels are critically involved in ramelteon-induced cardioprotection...
August 2018: Journal of Cardiovascular Pharmacology
Maedeh Arabian, Nahid Aboutaleb, Mansoureh Soleimani, Marjan Ajami, Rouhollah Habibey, Hamidreza Pazoki-Toroudi
PURPOSE: Pharmacologic preconditioning, through activating several mechanisms and mediators, can increase the tolerance of different tissues against ischemia/reperfusion (I/R) injury. Recent studies have shown that morphine preconditioning has protective effects in different organs, especially in the heart. Nevertheless, its mechanisms are not well elucidated in the brain. The present study aimed to clarify whether the activation of mitochondrial KATP (mKATP) channels in chronic morphine (CM) preconditioning could decrease hippocampus damage following I/R injury...
December 6, 2017: Advances in Medical Sciences
Young-Ho Jang, June-Hong Kim, Yong-Cheol Lee
BACKGROUND: Mitochondrial ATP-sensitive potassium (mKATP) channels play a role in reperfusion arrhythmias (RAs) in ischemia-reperfusion (I/R) injury. Evidence suggests that remote ischemic preconditioning (RIPC) reduces RAs, however not much is known on the mechanistic role of mKATP in RIPC. We evaluated whether mKATP channels are associated with reducing arrhythmia and infarct size in RIPC. METHODS: Isolated rat hearts received 30 minutes of regional ischemia followed by 2 hours of reperfusion through the Langendorff perfusion system...
February 2017: Anesthesiology and Pain Medicine
Anatoly A Starkov, Christos Chinopoulos, Natalia N Starkova, Csaba Konrad, Gergely Kiss, Anna Stepanova, Vasily N Popov
We demonstrate a suppression of ROS production and uncoupling of mitochondria by exogenous citrate in Mg2+ free medium. Exogenous citrate suppressed H2 O2 emission and depolarized mitochondria. The depolarization was paralleled by the stimulation of respiration of mitochondria. The uncoupling action of citrate was independent of the presence of sodium, potassium, or chlorine ions, and it was not mediated by the changes in permeability of the inner mitochondrial membrane to solutes. The citrate transporter was not involved in the citrate effect...
February 2017: Journal of Bioenergetics and Biomembranes
Malgorzata Slocińska, Grzegorz Rosinski, Wieslawa Jarmuszkiewicz
It has been evidenced that mitochondrial uncoupling protein 4 (UCP4) and ATP-regulated potassium channel (mKATP channel) of insect Gromphadorhina coqereliana mitochondria decrease superoxide anion production. We elucidated whether the two energy-dissipating systems work together on a modulation of superoxide level in cockroach mitochondria. Our data show that the simultaneous activation of UCP4 by palmitic acid and mKATP channel by pinacidil revealed a cumulative effect on weakening mitochondrial superoxide formation...
2016: Protein and Peptide Letters
Alireza Imani, Maryam Khansari, Yaser Azizi, Kamran Rakhshan, Mahdieh Faghihi
Postconditioning is a simple and safe strategy for cardioprotection and infarct size limitation. Our previous study showed that oxytocin (OT) exerts postconditioning effect on ischemic/reperfused isolated rat heart. The aim of this study was to investigate the involvement of OT receptor, mitochondrial ATP-sensitive potassium channel (mKATP), nitric oxide (NO) and cyclooxygenase (COX) pathways in OT postconditioning. Isolated rat hearts were divided into10 groups and underwent 30 min of regional ischemia followed by 120 min of reperfusion (n =6)...
August 2015: Acta Medica Iranica
Chuiliang Liu, Yanhui Liu, Zhiwen Shen, Liping Miao, Kun Zhang, Fei Wang, Yujuan Li
Ischemic preconditioning (IPC) has been considered to be a potential therapy to reduce ischemia-reperfusion injury (IRI) since the 1980s. Our previous study indicated that sevoflurane preconditioning (SPC) also reduced intestinal IRI in rats. However, whether the protective effect of SPC is similar to IPC and the mechanisms of SPC are unclear. Thus, we compared the efficacy of SPC and IPC against intestinal IRI and the role of protein kinase C (PKC) and mitochondrial ATP-sensitive potassium channel (mKATP) in SPC...
2015: PloS One
Alexandra Petruş, Oana M Duicu, Adrian Sturza, Lavinia Noveanu, Loránd Kiss, Maria Dănilă, István Baczkó, Danina M Muntean, Norbert Jost
A substantial body of evidence indicates that pharmacological activation of mitochondrial ATP-sensitive potassium channels (mKATP) in the heart is protective in conditions associated with ischemia/reperfusion injury. Several mechanisms have been postulated to be responsible for cardioprotection, including the modulation of mitochondrial respiratory function. The aim of the present study was to characterize the dose-dependent effects of novel synthetic benzopyran analogues, derived from a BMS-191095, a selective mKATP opener, on mitochondrial respiration and reactive oxygen species (ROS) production in isolated rat heart mitochondria...
September 2015: Canadian Journal of Physiology and Pharmacology
Erik Helgeland, Lars Breivik, Balindiwe J Sishi, Anna-Mart Engelbrecht, Anne K Jonassen
OBJECTIVES: It has previously been demonstrated that 15-min continuous insulin infusion at immediate reperfusion affords cardioprotection. This study sought to reduce the treatment time of insulin and test if intermittent insulin infusions can mimic ischemic postconditioning. DESIGN: In a Langendorff perfused rat heart model of regional ischemia, hearts were at the onset of reperfusion subjected to either 5- or 1-min continuous insulin infusion or 3 × 30 s intermittent insulin infusions (InsPost); with or without inhibitors of Akt (SH-6), p70s6-kinase (rapamycin), mitochondrial ATP-sensitive potassium channels (5-hydroxydecanoic acid [5-HD]), or a scavenger of reactive oxygen species (ROS; 2-mercaptopropionyl glycine [MPG])...
2015: Scandinavian Cardiovascular Journal: SCJ
Alejandra M Yeves, Claudia I Caldiz, Ernesto A Aiello, María C Villa-Abrille, Irene L Ennis
BACKGROUND: Reactive oxygen species, such as superoxide, are being increasingly recognized as key components of a vast array of signaling pathways. Angiotensin II is a well-recognized stimulus for superoxide production through NADPH oxidase activation and opening of the mitochondrial ATP-sensitive potassium channels (mKATP). A role for this mechanism has been proposed to explain several physiological effects of the peptide. The aim of this study was to evaluate the involvement of this mechanism in the inotropic response to 100nmol/L angiotensin II...
July 2015: Cardiovascular Pathology: the Official Journal of the Society for Cardiovascular Pathology
Daisuke Sunaga, Masaya Tanno, Atsushi Kuno, Satoko Ishikawa, Makoto Ogasawara, Toshiyuki Yano, Takayuki Miki, Tetsuji Miura
Loss of mitochondrial membrane potential (ΔΨm) is known to be closely linked to cell death by various insults. However, whether acceleration of the ΔΨm recovery process prevents cell necrosis remains unclear. Here we examined the hypothesis that facilitated recovery of ΔΨm contributes to cytoprotection afforded by activation of the mitochondrial ATP-sensitive K+ (mKATP) channel or inactivation of glycogen synthase kinase-3β (GSK-3β). ΔΨm of H9c2 cells was determined by tetramethylrhodamine ethyl ester (TMRE) before or after 1-h exposure to antimycin A (AA), an inducer of reactive oxygen species (ROS) production at complex III...
2014: PloS One
Chaoqin Xie, Justin Kauffman, Fadi G Akar
BACKGROUND: Mitochondrial permeability transition pore (mPTP) opening is a terminal event leading to mitochondrial dysfunction and cell death under conditions of oxidative stress (OS). However, mPTP blockade with cyclosporine A (CsA) has shown variable efficacy in limiting post-ischemic dysfunction and arrhythmias. We hypothesized that strong feedback between energy dissipating (mPTP) and cardioprotective (mKATP) channels determine vulnerability to OS. METHODS AND RESULTS: Guinea pig hearts (N = 61) were challenged with H2O2 (200 μM) to elicit mitochondrial membrane potential (ΔΨm) depolarization...
2014: Frontiers in Physiology
David James Dukoff, David William Hogg, Peter John Hawrysh, Leslie Thomas Buck
Oxygen deprivation triggers excitotoxic cell death in mammal neurons through excessive calcium loading via over-activation of N-methyl-d-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors. This does not occur in the western painted turtle, which overwinters for months without oxygen. Neurological damage is avoided through anoxia-mediated decreases in NMDA and AMPA receptor currents that are dependent upon a modest rise in intracellular Ca(2+) concentrations ([Ca(2+)]i) originating from mitochondria...
September 15, 2014: Journal of Experimental Biology
Theodore Kalogeris, Yimin Bao, Ronald J Korthuis
Reductions in the blood supply produce considerable injury if the duration of ischemia is prolonged. Paradoxically, restoration of perfusion to ischemic organs can exacerbate tissue damage and extend the size of an evolving infarct. Being highly metabolic organs, the heart and brain are particularly vulnerable to the deleterious effects of ischemia/reperfusion (I/R). While the pathogenetic mechanisms contributing to I/R-induced tissue injury and infarction are multifactorial, the relative importance of each contributing factor remains unclear...
2014: Redox Biology
Hongzhu Li, Can Wei, Jun Gao, Shuzhi Bai, Hongxia Li, Yajun Zhao, Hong Li, Liping Han, Ye Tian, Guangdong Yang, Rui Wang, Lingyun Wu, Changqing Xu
The physiological and pathological roles of dopamine D2 receptors (DR2) in the regulation of cardiovacular functions have been recognized. DR2 activation protects hypoxia/reoxygenation (H/R)-induced cardiomyocyte injury and apoptosis, and ischemic post-conditioning (PC) plays a critical role in cardioprotection as well; however the involvement of the DR2 activation in the PC-induced cardioprotection is unknown. In the present study, we found that the H/R increased the expressions of DR2 mRNA and protein in cardiomyocytes, which were significantly enhanced by PC...
April 15, 2014: Experimental Cell Research
M B Nolly, C I Caldiz, A M Yeves, M C Villa-Abrille, P E Morgan, Nicolas Amado Mondaca, Enrique L Portiansky, G E Chiappe de Cingolani, H E Cingolani, I L Ennis
Mineralocorticoid receptor (MR) antagonists decrease morbidity and mortality in heart failure patients for whom oxidative stress is usual; however, the underlying mechanism for this protection is unclear. Since aldosterone stimulates reactive oxygen species (ROS) production in several tissues, we explored its effect and the intracellular pathway involved in the rat myocardium. Aldosterone dose-dependently increased O2(-) production in myocardial slices. At 10 nmol/L, aldosterone increased O2(-) to 165 ± 8...
February 2014: Journal of Molecular and Cellular Cardiology
Jason N Peart, Salvatore Pepe, Melissa E Reichelt, Nikkie Beckett, Louise See Hoe, Victoria Ozberk, Ingrid R Niesman, Hemal H Patel, John P Headrick
Changes in cytoprotective signaling may influence cardiac aging, and underpin sensitization to ischemic insult and desensitization to 'anti-ischemic' therapies. We tested whether age-dependent shifts in ischemia-reperfusion (I-R) tolerance in murine and human myocardium are associated with reduced efficacies and coupling of membrane, cytoplasmic and mitochondrial survival-signaling. Hormesis (exemplified in ischemic preconditioning; IPC) and expression of proteins influencing signaling/stress-resistance were also assessed in mice...
February 2014: Experimental Gerontology
Jung Il Lee, Kyung Wook Nha, Jin Soo Suh, Suk Kyu Choo, Jung Ho Park, Jong Woong Park
The authors investigated whether a remote postconditioning (remote post-con) procedure attenuated skeletal muscle ischemia/reperfusion (I/R) injury. We determined the optimal protocol of remote post-con and investigated its mechanism. Ischemia was induced for 3 hours in rat left hindlimb and three protocols of remote post-con were applied in right hindlimb just before the end of ischemia. The first (10-second group) involved two cycles of 10 seconds of occlusion followed by 10 seconds of reperfusion. The second (5-minute group) involved two cycles of 5 minutes of occlusion/reperfusion...
November 2013: Journal of Reconstructive Microsurgery
Andrew P Wojtovich, William R Urciuoli, Shampa Chatterjee, Aron B Fisher, Keith Nehrke, Paul S Brookes
ATP-sensitive K(+) (KATP) channels that contain K(+) inward rectifier subunits of the 6.2 isotype (Kir6.2) are important regulators of the cardiac response to ischemia-reperfusion (I/R) injury. Opening of these channels is implicated in the cardioprotective mechanism of ischemic preconditioning (IPC), but debate surrounds the contribution of surface KATP (sKATP) versus mitochondrial KATP (mKATP) channels. While responses to I/R injury and IPC have been examined in Kir6.2(-/-) mice before, breeding methods and other technical obstacles may have confounded interpretations...
June 1, 2013: American Journal of Physiology. Heart and Circulatory Physiology
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