Crosstalk signaling between mitochondrial Ca2+ and ROS

Feissner, Robert E.; Skalska, Jolanta; Gaum, Winston E.; Sheu, Shey‐Shing

doi:10.2741/3303

Cited by 370 publications

(315 citation statements)

References 251 publications

(257 reference statements)

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“…[124][125][126][127][128] ROS, through the regulation of hypoxia-inducible factor-1, are also important in O 2 sensing, 125 which is essential for maintaining normal O 2 homeostasis. In pathological conditions ROS are involved in inflammation, endothelial dysfunction, cell proliferation, migration and activation, extracellular matrix deposition, fibrosis, angiogenesis and vascular remodeling [129][130][131] ( Figure 3). …”

Section: Ros and Vascular Biology In Hypertensionmentioning

confidence: 99%

Reactive oxygen species and vascular biology: implications in human hypertension

2010

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Increased vascular production of reactive oxygen species (ROS; termed oxidative stress) has been implicated in various chronic diseases, including hypertension. Oxidative stress is both a cause and a consequence of hypertension. Although oxidative injury may not be the sole etiology, it amplifies blood pressure elevation in the presence of other pro-hypertensive factors. Oxidative stress is a multisystem phenomenon in hypertension and involves the heart, kidneys, nervous system, vessels and possibly the immune system. Compelling experimental and clinical evidence indicates the importance of the vasculature in the pathophysiology of hypertension and as such much emphasis has been placed on the (patho)biology of ROS in the vascular system. A major source for cardiovascular, renal and neural ROS is a family of non-phagocytic nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (Nox), including the prototypic Nox2 homolog-based NADPH oxidase, as well as other Noxes, such as Nox1 and Nox4. Nox-derived ROS is important in regulating endothelial function and vascular tone. Oxidative stress is implicated in endothelial dysfunction, inflammation, hypertrophy, apoptosis, migration, fibrosis, angiogenesis and rarefaction, important processes involved in vascular remodeling in hypertension. Despite a plethora of data implicating oxidative stress as a causative factor in experimental hypertension, findings in human hypertension are less conclusive. This review highlights the importance of ROS in vascular biology and focuses on the potential role of oxidative stress in human hypertension.

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Section: Ros and Vascular Biology In Hypertensionmentioning

confidence: 99%

Reactive oxygen species and vascular biology: implications in human hypertension

2010

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“…Changes in structure caused by oxidizing amino acid residues can change the activity of enzymes and ion transporters [30]. In the context of Ca 2+ signalling, redox state and ROS can stimulate, as well as inhibit Ca 2+ channels/pumps/exchangers, generally increasing Ca 2+ channel activity and inhibiting Ca 2+ pumps [31]. Precisely, ROS can directly, or indirectly through changes in cell redox homeostasis, oxidize redox-sensing thiol groups on the ryanodine receptors leading to channel stimulation.…”

Section: Signalling Roles Of Ca2+ and Rosmentioning

confidence: 99%

“…Inositol-1,4,5-triphosphate receptor channels are the primary Ca 2+ endoplasmic reticulum release channels, while sarco/endoplasmic reticulum and plasma membrane Ca 2+ ATPase are Ca 2+ re-uptake pumps. Furthermore, there is also an important plasma membrane Na + /Ca 2+ exchanger [31]. Its function is also modulated by oxidation.…”

Section: Signalling Roles Of Ca2+ and Rosmentioning

confidence: 99%

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The Role of Reactive Species in Epileptogenesis and Influence of Antiepileptic Drug Therapy on Oxidative Stress

Martinc

Grabnar²,

Vovk³

2012

Current Neuropharmacology

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Epilepsy is considered one of the most common neurological disorders. The focus of this review is the acquired form of epilepsy, with the development process consisting of three major phases, the acute injury phase, the latency epileptogenesis phase, and the phase of spontaneous recurrent seizures. Nowadays, an increasing attention is paid to the possible interrelationship between oxidative stress resulting in disturbance of physiological signalling roles of calcium and free radicals in neuronal cells and mitochondrial dysfunction, cell damage, and epilepsy. The positive stimulation of mitochondrial calcium signals by reactive oxygen species and increased reactive oxygen species generation resulting from increased mitochondrial calcium can lead to a positive feedback loop. We propose that calcium can pose both, physiological and pathological effects of mitochondrial function, which can lead in neuronal cell death and consequent epileptic seizures. Various antiepileptic drugs may impair the endogenous antioxidative ability to prevent oxidative stress. Therefore, some antiepileptic drugs, especially from the older generation, may trigger oxygen-dependent tissue injury. The prooxidative effects of these antiepileptic drugs might lead to enhancement of seizure activity, resulting in loss of their efficacy or apparent functional tolerance and undesired adverse effects. Additionally, various reactive metabolites of antiepileptic drugs are capable of covalent binding to macromolecules which may lead to deterioration of the epileptic seizures and systemic toxicity. Since neuronal loss seems to be one of the major neurobiological abnormalities in the epileptic brain, the ability of antioxidants to attenuate seizure generation and the accompanying changes in oxidative burden, further support an important role of antioxidants as having a putative antiepileptic potential.

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“…Indeed, ROS/RNS are known to inhibit SERCA pumps and activate RyRs and IP 3 Rs. 14,15 Moderate levels of ROS/RNS modify Ca 2C oscillations Having established that massive ROS/RNS production by AlClPc photoactivation abolishes Ca 2C oscillations in MIN6 cells, we turned our attention to the effects of moderate ROS/ RNS levels. When photoactivating AlClPc with 10% LED intensity we observed that Ca 2C oscillations typically persisted, but with a modified profile.…”

mentioning

confidence: 99%

Reactive oxygen and nitrogen species disturb Ca²⁺oscillations in insulin-secreting MIN6 β-cells

Antonucci

Tagliavini

Pedersen

2015

Islets

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Keywords: calcium pumps, mathematical modeling, pulsatile insulin secretion, photosensitizer, ROS/RNS Abbreviations: AlClPc, Aluminum Phthalocyanine Chloride; CICR, calcium-induced calcium release; CuFL, selective turn-on fluorescent NO reporter formed by a Cu(II) complex of a fluorescein modified with an appended metal-chelating ligand (FL); ER, endoplasmic reticulum; IP 3 R, inositol triphospate receptor; MitoSOX, mitochondrial superoxide indicator; NO, nitric oxide; PMCA, plasma membrane Ca 2C ATPase; RNS, reactive nitrogen species; ROS, reactive oxygen species; RyR, ryanodine receptor; SERCA, Sarcoplasmic/endoplasmic reticulum Ca 2C ATPase; TEA, tetraethylammonium; Tg, thapsigargin.Disturbances in pulsatile insulin secretion and Ca 2C oscillations in pancreatic b-cells are early markers of diabetes, but the underlying mechanisms are still incompletely understood. Reactive oxygen/nitrogen species (ROS/RNS) are implicated in reduced b-cell function, and ROS/RNS target several Ca 2C pumps and channels. Thus, we hypothesized that ROS/RNS could disturb Ca 2C oscillations and downstream insulin pulsatility. We show that ROS/RNS production by photoactivation of aluminum phthalocyanine chloride (AlClPc) abolish or accelerate Ca 2C oscillations in the MIN6 b-cell line, depending on the amount of ROS/RNS. Application of the sarcoplasmic/endoplasmic reticulum Ca 2C ATPase (SERCA) inhibitor thapsigargin modifies the Ca 2C response to high concentrations of ROS/RNS. Further, thapsigargin produces effects that resemble those elicited by moderate ROS/RNS production. These results indicate that ROS/RNS interfere with endoplasmic reticulum Ca 2C handling. This idea is supported by theoretical studies using a mathematical model of Ca 2C handling adapted to MIN6 cells. Our results suggest a putative link between ROS/RNS and disturbed pulsatile insulin secretion. IntroductionInsulin is secreted from the pancreatic b-cells in distinct pulses 1,2 and disturbed pulsatile insulin release has been suggested to be an early marker of diabetes. 3 These bursts of insulin are driven by underlying oscillations in electrical activity and cytosolic Ca 2C levels, which periodically trigger Ca 2C -regulated exocytosis. 4 Importantly, secretory pulses are more effective than constant insulin levels in lowering plasma glucose levels. 3,5,6 In particular, hepatic signaling is highly sensitive to whether insulin is released in pulses, 7 leading to the suggestion that insulin resistance in the liver is secondary to disturbed pulsatile insulin release. 8 Thus, a deeper understanding of oscillatory b-cell activity and its disturbance has clinical relevance.Disturbed insulin secretion and diabetes have been associated with b-cell damage caused by reactive oxygen species (ROS). 9 However, ROS have also been shown to exert a stimulating short-term effect on insulin release. 10 Hence, ROS may act as a double-edged sword: moderate and short-term elevations play a positive signaling role augmenting insulin secretion, but prolonged exposure to elevated ROS...

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Crosstalk signaling between mitochondrial Ca2+ and ROS

Cited by 370 publications

References 251 publications

Reactive oxygen species and vascular biology: implications in human hypertension

Reactive oxygen species and vascular biology: implications in human hypertension

The Role of Reactive Species in Epileptogenesis and Influence of Antiepileptic Drug Therapy on Oxidative Stress

Reactive oxygen and nitrogen species disturb Ca²⁺oscillations in insulin-secreting MIN6 β-cells

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Crosstalk signaling between mitochondrial Ca2+ and ROS

Cited by 370 publications

References 251 publications

Reactive oxygen species and vascular biology: implications in human hypertension

Reactive oxygen species and vascular biology: implications in human hypertension

The Role of Reactive Species in Epileptogenesis and Influence of Antiepileptic Drug Therapy on Oxidative Stress

Reactive oxygen and nitrogen species disturb Ca2+oscillations in insulin-secreting MIN6 β-cells

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Reactive oxygen and nitrogen species disturb Ca²⁺oscillations in insulin-secreting MIN6 β-cells