Peroxynitrite Mediates Disruption of Ca2+ Homeostasis by Carbon Monoxide via Ca2+ ATPase Degradation

Hettiarachchi, Nishani T.; Boyle, John P.; Bauer, Claudia; Dallas, Mark L.; Pearson, Hugh A.; Hara, Shuichi; Gamper, Nikita; Peers, Chris

doi:10.1089/ars.2011.4398

Cited by 13 publications

(16 citation statements)

References 49 publications

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“…Thus, in cardiomyocytes (24), HEK293 cells (Fig. 4), and other cell types (48), CO increased intracellular NO levels, and in each case, the effects of CO were prevented or dramatically reduced by inhibiting NO formation. However, it is equally noteworthy that although the augmentation of the late current by CO could be mimicked by an NO donor (24), the inhibition of the peak current could not (Fig.…”

Section: Discussionmentioning

confidence: 87%

“…Experimentally, both positive and negative effects of CO can be demonstrated. Thus, CO can reduce neuronal damage arising from focal ischemia (47) yet can be detrimental through disruption of neuronal Ca 2+ homeostasis (48). In the heart, endogenous CO arising from elevated HO-1 expression limits the cellular damage caused by ischemia/reperfusion injury in mice (6–8), and similar protective results have been recently reported using the CO donor, CORM-3 (24).…”

Section: Discussionmentioning

confidence: 99%

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Inhibition of the Cardiac Na+ Channel Nav1.5 by Carbon Monoxide

Elíes

Dallas

Boyle

et al. 2014

Journal of Biological Chemistry

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Background: CO poisoning causes cardiac arrhythmias, in part via modulation of the cardiac Na+ channel, Nav1.5.Results: CO inhibition of peak recombinant Nav1.5 current occurs via nitric oxide formation and is also dependent on channel redox state.Conclusion: CO inhibits peak recombinant Nav1.5 current via a mechanism distinct from activation of the late Na+ current.Significance: CO may induce Brugada-like arrhythmias via inhibition of peak Na+ current.

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Section: Discussionmentioning

confidence: 87%

Section: Discussionmentioning

confidence: 99%

Inhibition of the Cardiac Na+ Channel Nav1.5 by Carbon Monoxide

Elíes

Dallas

Boyle

et al. 2014

Journal of Biological Chemistry

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“…refs 66, 67) and can in some instances itself be damaging through formation of ONOO – , as shown in neuroblastoma (SH-SY5Y) cells. 66 The source of ROS and / or the specific cell type is therefore likely to be key to outcomes. Clearly, the present study shows that CO is protective against A β 1–42 toxicity in astrocytes, and this is mediated through suppression of NADPH oxidase activity.…”

Section: Discussionmentioning

confidence: 99%

“…36 Furthermore, CO can increase formation of NO in various cell types (e.g. refs 66, 67) and can in some instances itself be damaging through formation of ONOO – , as shown in neuroblastoma (SH-SY5Y) cells. 66 The source of ROS and / or the specific cell type is therefore likely to be key to outcomes.…”

Section: Discussionmentioning

confidence: 99%

Heme oxygenase-1 derived carbon monoxide suppresses Aβ1–42 toxicity in astrocytes

et al. 2017

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Neurodegeneration in Alzheimer’s disease (AD) is extensively studied, and the involvement of astrocytes and other cell types in this process has been described. However, the responses of astrocytes themselves to amyloid β peptides ((Aβ; the widely accepted major toxic factor in AD) is less well understood. Here, we show that Aβ(1-42) is toxic to primary cultures of astrocytes. Toxicity does not involve disruption of astrocyte Ca2+ homeostasis, but instead occurs via formation of the toxic reactive species, peroxynitrite. Thus, Aβ(1-42) raises peroxynitrite levels in astrocytes, and Aβ(1-42) toxicity can be inhibited by antioxidants, or by inhibition of nitric oxide (NO) formation (reactive oxygen species (ROS) and NO combine to form peroxynitrite), or by a scavenger of peroxynitrite. Increased ROS levels observed following Aβ(1-42) application were derived from NADPH oxidase. Induction of haem oxygenase-1 (HO-1) protected astrocytes from Aβ(1-42) toxicity, and this protective effect was mimicked by application of the carbon monoxide (CO) releasing molecule CORM-2, suggesting HO-1 protection was attributable to its formation of CO. CO suppressed the rise of NADPH oxidase-derived ROS caused by Aβ(1-42). Under hypoxic conditions (0.5% O2, 48 h) HO-1 was induced in astrocytes and Aβ(1-42) toxicity was significantly reduced, an effect which was reversed by the specific HO-1 inhibitor, QC-15. Our data suggest that Aβ(1-42) is toxic to astrocytes, but that induction of HO-1 affords protection against this toxicity due to formation of CO. HO-1 induction, or CO donors, would appear to present attractive possible approaches to provide protection of both neuronal and non-neuronal cell types from the degenerative effects of AD in the central nervous system.

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“…CO also inhibits the calcium influx induced by ADP and thrombin, although it was not known whether the Ca 2+ entry was mediated through SOCE or ROCE [48]. On the contrary, CO released by CORM-2 enhanced the Tg-induced capacitative calcium entry in SH-SY5Y cells, a human neuroblastoma cell line, possibly by inhibiting Ca 2+ extrusion via plasma membrane Ca 2+ -ATPase through a nitric oxide-dependent increase in reactive oxygen species [49]. Therefore, CO causes diverse modulatory effects on the calcium entry pathway and the effect is probably cell-type specific.…”

Section: Discussionmentioning

confidence: 99%

Regulation of Intracellular Calcium by Carbon Monoxide in Human Bronchial Epithelial Cells

Zhang¹,

Yip²,

Ko³

2017

Cell Physiol Biochem

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Background/Aims: Carbon monoxide (CO) is an important autocrine/paracrine messenger involved in a variety of physiological and pathological processes. This study aimed to investigate the regulatory role of CO released by CO-releasing molecule-2 (CORM-2) in a P2Y receptor-mediated calcium-signaling pathway in the human bronchial epithelial cell line, 16HBE14o-. Methods: Intracellular calcium ([Ca²⁺]_i) was measured by fura-2 microspectrofluorimetry. D-myo-inositol-1-phosphate (IP₁) levels and cGMP-dependent protein kinase activity (PKG) were also quantified. Results: The exogenous application of CORM-2 increased both intracellular Ca²⁺ and IP₁, which are inhibited by U73122, a phospholipase C (PLC) inhibitor. In contrast, the P2Y₂/P2Y₄ receptor-mediated intracellular Ca²⁺ release and influx induced by UTP were inhibited in the presence of CORM-2. However, CORM-2 did not affect the store-operated Ca²⁺ entry (SOCE) induced by thapsigargin (Tg). Moreover, the inhibitory effect of CORM-2 on UTP-induced calcium increase could be attenuated by a soluble guanylyl cyclase (sGC) inhibitor, 1H-[1,2,4]oxadiazolo[4,3,-a]quinoxalin-1-one (ODQ), or a Protein Kinase G (PKG) inhibitor, KT5823, suggesting the involvement of sGC/PKG signaling in this process. Conclusion: CORM-2 serves a dual role in modulating [Ca²⁺]_i in 16HBE14o- cells. Thus, CO released by CORM-2 may act as a regulator of calcium homeostasis in human airway epithelia. These findings help further elucidate the function of CO in many physiological and pathological conditions.

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Peroxynitrite Mediates Disruption of Ca²⁺ Homeostasis by Carbon Monoxide via Ca²⁺ ATPase Degradation

Abstract: CO stimulates formation of NO and reactive oxygen species which, via peroxynitrite formation, inhibit Ca(2+) extrusion via PMCA, leading to disruption of Ca(2+) signaling. We propose this contributes to the neurological damage associated with CO toxicity.

Cited by 13 publications

References 49 publications

Inhibition of the Cardiac Na+ Channel Nav1.5 by Carbon Monoxide

Inhibition of the Cardiac Na+ Channel Nav1.5 by Carbon Monoxide

Heme oxygenase-1 derived carbon monoxide suppresses Aβ1–42 toxicity in astrocytes

Regulation of Intracellular Calcium by Carbon Monoxide in Human Bronchial Epithelial Cells

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