Protective effects of HOE642, a selective sodium-hydrogen exchange subtype 1 inhibitor, on cardiac ischaemia and reperfusion

Scholz, Wolfgang

doi:10.1016/0008-6363(96)88579-8

Cited by 191 publications

(155 citation statements)

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“…HOE 642 (0.5 mg/kg) was administered intraperitoneally at 10 min, 24 and 48 h after HI (n = 8; 6 M, 2 F). Due to the short half-life of HOE 642, it was administered at multiple time points (half-life: 40 min in rats) [13]. The HI vehicle control animals received an equal volume of saline at the same time points (n = 9; 6 F, 3 M).…”

Section: Methodsmentioning

confidence: 99%

Chronic Neurological Deficits in Mice after Perinatal Hypoxia and Ischemia Correlate with Hemispheric Tissue Loss and White Matter Injury Detected by MRI

et al. 2011

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We investigated the effects of perinatal hypoxia-ischemia (HI) on brain injury and neurological functional outcome at postnatal day (P)30 through P90. HI was induced by exposing P9 mice to 8% O₂ for 55 min using the Vannucci HI model. Following HI, mice were treated with either vehicle control or Na⁺/H⁺ exchanger isoform 1 (NHE1) inhibitor HOE 642. The animals were examined by the accelerating rotarod test at P30 and the Morris water maze (MWM) test at P60. T₂-weighted MRI was conducted at P90. Diffusion tensor imaging (DTI) was subsequently performed in ex vivo brains, followed by immunohistochemical staining for changes in myelin basic protein (MBP) and neurofilament protein expression in the corpus callosum (CC). Animals at P30 after HI showed deficits in motor and spatial learning. T₂ MRI detected a wide spectrum of brain injury in these animals. A positive linear correlation was observed between learning deficits and the degree of tissue loss in the ipsilateral hemisphere and hippocampus. Additionally, CC DTI fractional anisotropy (FA) values correlated with MBP expression. Both FA and MBP values correlated with performance on the MWM test. HOE 642-treated mice exhibited improved spatial learning and memory, and less white matter injury in the CC. These findings suggest that HI-induced cerebral atrophy and CC injury contribute to the development of deficits in learning and memory, and that inhibition of NHE1 is neuroprotective in part by reducing white matter injury. T₂-weighted MRI and DTI are useful indicators of functional outcome after perinatal HI.

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Section: Methodsmentioning

confidence: 99%

Chronic Neurological Deficits in Mice after Perinatal Hypoxia and Ischemia Correlate with Hemispheric Tissue Loss and White Matter Injury Detected by MRI

et al. 2011

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“…Cariporide, which is a high selective and low cytotoxic NHE1 inhibitor [22], was used to decrease the pH i . This study was aimed to explore the effect of decreased pH i on the differentiation of hUC-MSCs and to explore the putative mechanism involved.…”

Section: Introductionmentioning

confidence: 99%

Decreased Intracellular pH Induced by Cariporide Differentially Contributes to Human Umbilical Cord-Derived Mesenchymal Stem Cells Differentiation

Gao

Zhang

Chang

et al. 2014

Cell Physiol Biochem

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Background/Aims: Na+/H+ exchanger 1 (NHE1) is an important regulator of intracellular pH (pH_i). High pH_i is required for cell proliferation and differentiation. Our previous study has proven that the pH_i of mesenchymal stem cells is higher than that of normal differentiated cells and similar to tumor cells. NHE1 is highly expressed in both mesenchymal stem cells and tumor cells. Targeted inhibition of NHE1 could induce differentiation of K562 leukemia cells. In the present paper we explored whether inhibition of NHE1 could induce differentiation of mesenchymal stem cells. Methods: MSCs were obtained from human umbilical cord and both the surface phenotype and functional characteristics were analyzed. Selective NHE1 inhibitor cariporide was used to treat human umbilical cord-derived mesenchymal stem cells (hUC-MSCs). The pH_i and the differentiation of hUC-MSCs were compared upon cariporide treatment. The putative signaling pathway involved was also explored. Results: The pH_i of hUC-MSCs was decreased upon cariporide treatment. Cariporide up-regulated the osteogenic differentiation of hUC-MSCs while the adipogenic differentiation was not affected. For osteogenic differentiation, β-catenin expression was up-regulated upon cariporide treatment. Conclusion: Decreased pH_i induced by cariporide differentially contributes to hUC-MSCs differentiation.

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“…Our previous study has shown that insulin action on GLUT4 translocation and NHE1 activity are intricately linked, demonstrated by the finding that NHE1 activity is required for optimal GLUT4 translocation [17]. Cariporide, an NHE inhibitor [22], prevented the insulin-induced cytosol alkalinization and the associated insulin-stimulated GLUT4 translocation and glucose uptake [17]. …”

Section: Introductionmentioning

confidence: 99%

Translocation of the Na+/H+ exchanger 1 (NHE1) in cardiomyocyte responses to insulin and energy-status signalling

Lawrence

Holman

Koumanov

2010

Biochemical Journal

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The Na+/H+ exchanger NHE1 is a highly regulated membrane protein that is required for pH homoeostasis in cardiomyocytes. The activation of NHE1 leads to proton extrusion, which is essential for counteracting cellular acidity that occurs following increased metabolic activity or ischaemia. The activation of NHE1 intrinsic catalytic activity has been well characterized and established experimentally. However, we have examined in the present study whether a net translocation of NHE1 to the sarcolemma of cardiomyocytes may also be involved in the activation process. We have determined the distribution of NHE1 by means of immunofluorescence microscopy and cell-surface biotinylation. We have discovered changes in the distribution of NHE1 that occur when cardiomyocytes are stimulated with insulin that are PI3K (phosphoinositide 3-kinase)-dependent. Translocation of NHE1 also occurs when cardiomyocytes are challenged by hypoxia, or inhibition of mitochondrial oxidative metabolism or electrically induced contraction, but these responses occur through a PI3K-independent process. As the proposed additional level of control of NHE1 through translocation was unexpected, we have compared this process with the well-established translocation of the glucose transporter GLUT4. In immunofluorescence microscopy comparisons, the translocation of NHE1 and GLUT4 to the sarcolemma that occur in response to insulin appear to be very similar. However, in basal unstimulated cells the two proteins are mainly located, with the exception of some co-localization in the perinuclear region, in distinct subcellular compartments. We propose that the mechanisms of translocation of NHE1 and GLUT4 are linked such that they provide spatially and temporally co-ordinated responses to cardiac challenges that necessitate re-adjustments in glucose transport, glucose metabolism and cell pH.

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Protective effects of HOE642, a selective sodium-hydrogen exchange subtype 1 inhibitor, on cardiac ischaemia and reperfusion

Cited by 191 publications

References 0 publications

Chronic Neurological Deficits in Mice after Perinatal Hypoxia and Ischemia Correlate with Hemispheric Tissue Loss and White Matter Injury Detected by MRI

Chronic Neurological Deficits in Mice after Perinatal Hypoxia and Ischemia Correlate with Hemispheric Tissue Loss and White Matter Injury Detected by MRI

Decreased Intracellular pH Induced by Cariporide Differentially Contributes to Human Umbilical Cord-Derived Mesenchymal Stem Cells Differentiation

Translocation of the Na+/H+ exchanger 1 (NHE1) in cardiomyocyte responses to insulin and energy-status signalling

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