Ischemia–reperfusion alters gene expression of Na+–K+ ATPase isoforms in rat heart

BackgroundAlthough AKI lacks effective therapeutic approaches, preventive strategies using preconditioning protocols, including caloric restriction and hypoxic preconditioning, have been shown to prevent injury in animal models. A better understanding of the molecular mechanisms that underlie the enhanced resistance to AKI conferred by such approaches is needed to facilitate clinical use. We hypothesized that these preconditioning strategies use similar pathways to augment cellular stress resistance.MethodsTo identify genes and pathways shared by caloric restriction and hypoxic preconditioning, we used RNA-sequencing transcriptome profiling to compare the transcriptional response with both modes of preconditioning in mice before and after renal ischemia-reperfusion injury.ResultsThe gene expression signatures induced by both preconditioning strategies involve distinct common genes and pathways that overlap significantly with the transcriptional changes observed after ischemia-reperfusion injury. These changes primarily affect oxidation-reduction processes and have a major effect on mitochondrial processes. We found that 16 of the genes differentially regulated by both modes of preconditioning were strongly correlated with clinical outcome; most of these genes had not previously been directly linked to AKI.ConclusionsThis comparative analysis of the gene expression signatures in preconditioning strategies shows overlapping patterns in caloric restriction and hypoxic preconditioning, pointing toward common molecular mechanisms. Our analysis identified a limited set of target genes not previously known to be associated with AKI; further study of their potential to provide the basis for novel preventive strategies is warranted. To allow for optimal interactive usability of the data by the kidney research community, we provide an online interface for user-defined interrogation of the gene expression datasets (http://shiny.cecad.uni-koeln.de:3838/IRaP/).

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Adrenomedullin Gene Expression in the Rat Heart is Stimulated by Acute Pressure Overload: Blunted Effect in Experimental Hypertension

Endocrinology ◽

10.1210/endo.138.6.9105 ◽

1997 ◽

Vol 138 (6) ◽

pp. 2632-2635 ◽

Cited By ~ 18

Author(s):

Hannu Romppanen ◽

Minna Marttila ◽

Jarkko Magga ◽

Olli Vuolteenaho ◽

Pietari Kinnunen ◽

...

Keyword(s):

Gene Expression ◽

Rat Heart ◽

Pressure Overload ◽

Experimental Hypertension

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Depression of Gap junctional gene expression after regional hepatic ischemia/reperfusion

Hepatology ◽

10.1016/0270-9139(95)94916-x ◽

1995 ◽

Vol 22 (4) ◽

pp. A298

Author(s):

A DEMAIO

Keyword(s):

Gene Expression ◽

Ischemia Reperfusion ◽

Hepatic Ischemia ◽

Hepatic Ischemia Reperfusion ◽

Gap Junctional

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Gypenosides alleviate myocardial ischemia-reperfusion injury via attenuation of oxidative stress and preservation of mitochondrial function in rat heart

Cell Stress and Chaperones ◽

10.1007/s12192-016-0669-5 ◽

2016 ◽

Vol 21 (3) ◽

pp. 429-437 ◽

Cited By ~ 23

Author(s):

Haijie Yu ◽

Qigang Guan ◽

Liang Guo ◽

Haishan Zhang ◽

Xuefeng Pang ◽

...

Keyword(s):

Oxidative Stress ◽

Myocardial Ischemia ◽

Reperfusion Injury ◽

Mitochondrial Function ◽

Rat Heart ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Myocardial Ischemia Reperfusion Injury ◽

Myocardial Ischemia Reperfusion

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Gene expression in response to ischemia-reperfusion (IR) in rat intestine

Gastroenterology ◽

10.1016/s0016-5085(98)81760-5 ◽

1998 ◽

Vol 114 ◽

pp. A435

Author(s):

KY. Yeh ◽

M. Yeh ◽

DN. Granger ◽

J. Glass

Keyword(s):

Gene Expression ◽

Ischemia Reperfusion ◽

Rat Intestine

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Abstract 104: Effects of Pinacidil and Ca 2 + on Sodium-loaded Rat Heart Mitochondria

Circulation Research ◽

10.1161/res.113.suppl_1.a104 ◽

2013 ◽

Vol 113 (suppl_1) ◽

Author(s):

Sergey M Korotkov ◽

Vladimir P Nesterov ◽

Irina V Brailovskaya ◽

Larisa V Emelyanova ◽

Svetlana A Konovalova ◽

...

Keyword(s):

Oxygen Consumption ◽

Rat Heart ◽

Mitochondrial Membrane ◽

Mitochondrial Permeability Transition ◽

Ischemia Reperfusion ◽

Potassium Acetate ◽

Heart Mitochondria ◽

Inner Mitochondrial Membrane ◽

Rat Heart Mitochondria ◽

Acetate Medium

Deterioration of the contractile parameters of the heart muscle caused by ischemia and followed reperfusion is known as the main postoperative complication which is related to Ca 2+ and Na + overload in cardiomyocytes and mitochondria. Pinacidil reduced the overload in ischemia/reperfusion experiments. The mechanism of this phenomenon is still not clear. We hypothesized that increased ion permeability of the inner mitochondrial membrane (IMM) followed drop of electrochemical potential (ΔΨ mito ) can reduce the calcium. The aim of the study was to elucidate the effect of pinacidil (100 μM) and Ca 2+ (100 μM ) on swelling, oxygen consumption and ΔΨ mito of isolated sodium-loaded rat heart mitochondria (RHM(Na)) energized glutamate and malate. Pinacidil significantly enchanced the permeability of IMM to protons in ammonium nitrate medium. Also increased swelling of RHM(Na) energized with substrates in potassium acetate medium revealed that pinacidil increased potassium transport into matrix. Pinacidil stimulated oxygen consumption of RHM(Na) in State 4 and detained Ca 2+ -induced dissipation of ΔΨ mito . Under condition of Ca 2+ and Na + overload simulating ischemia/reperfusion, RHM(Na) oxygen consumption was not affected with pinacidil in State 3 and in the presence of 2,4-dinitrophenol. Cyclosporin A and ADP, the inhibitors of mitochondrial permeability transition pore (MPTP), markedly decreased Ca 2+ - induced swelling of RHM(Na) in nitrate ammonium or potassium acetate medium in the presence of pinacidil. Carboxyatractyloside, an inhibitor of cytosolic side-specific adenine nucleotide translocase, eliminated a pinacidil-stimulated oxygen consumption of succinate-energized RHMNa in State 4 regardless of the presence of Ca 2+ . Pinacidil was also concluded to accelerat potassium flux into energized RHM(Na) and promot MPTP opening in the low conduction state. Based on our data we suggested that the effect of pharmacological preconditioning induced by pinacidil could be due to it’s direct effect on mitochondria which is connected with above stimulation of the potassium permeability of the inner mitochondrial membrane and following reduce of the ΔΨ mito that thus prevent calcium overload of cardiomyocytes after ischemia/reperfusion in turn.

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