The Impact of DIDS-Induced Inhibition of Voltage-Dependent Anion Channels (VDAC) on Cellular Response of Lymphoblastoid Cells to Ionizing Radiation

Skonieczna, Magdalena; Cieślar-Pobuda, Artur; Saenko, Yury; Foksiński, Marek; Oliński, Ryszard; Rzeszowska-Wolny, Joanna; Wiecheć, Emilia

doi:10.2174/1573406413666170421102353

Cited by 42 publications

(27 citation statements)

References 45 publications

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“…) and voltage‐dependent anion channel in mitochondria (Skonieczna et al . ). The K + channel agonists ML277 and NS1643 are not very widely used and therefore data on their specificity are scarce.…”

Section: Discussionmentioning

confidence: 97%

“…DIDS, for example, is not especially selective for CaCCs. DIDS is a widely used inhibitor of cellular anion conductances and was demonstrated to suppress various Cl − channels (Duan & Nattel, 1994), the Cl − /HCO 3 − exchanger (Helbig et al 1988) and voltage-dependent anion channel in mitochondria (Skonieczna et al 2017). The K + channel agonists ML277 and NS1643 are not very widely used and therefore data on their specificity are scarce.…”

Section: Figure 9 K + Channel Agonists Have No Effect On Cat Alternamentioning

confidence: 99%

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Action potential shortening rescues atrial calcium alternans

Kanaporis

Kalik

Blatter

2018

The Journal of Physiology

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Key points Cardiac alternans refers to a beat‐to‐beat alternation in contraction, action potential (AP) morphology and Ca2+ transient (CaT) amplitude, and represents a risk factor for cardiac arrhythmia, including atrial fibrillation. We developed strategies to pharmacologically manipulate the AP waveform with the goal to reduce or eliminate the occurrence of CaT and contraction alternans in atrial tissue. With combined patch‐clamp and intracellular Ca2+ measurements we investigated the effect of specific ion channel inhibitors and activators on alternans. In single rabbit atrial myocytes, suppression of Ca2+‐activated Cl− channels eliminated AP duration alternans, but prolonged the AP and failed to eliminate CaT alternans. In contrast, activation of K+ currents (IKs and IKr) shortened the AP and eliminated both AP duration and CaT alternans. As demonstrated also at the whole heart level, activation of K+ conductances represents a promising strategy to suppress alternans, and thus reducing a risk factor for atrial fibrillation. Abstract At the cellular level alternans is observed as beat‐to‐beat alternations in contraction, action potential (AP) morphology and magnitude of the Ca2+ transient (CaT). Alternans is a well‐established risk factor for cardiac arrhythmia, including atrial fibrillation. This study investigates whether pharmacological manipulation of AP morphology is a viable strategy to reduce the risk of arrhythmogenic CaT alternans. Pacing‐induced AP and CaT alternans were studied in rabbit atrial myocytes using combined Ca2+ imaging and electrophysiological measurements. Increased AP duration (APD) and beat‐to‐beat alternations in AP morphology lowered the pacing frequency threshold and increased the degree of CaT alternans. Inhibition of Ca2+‐activated Cl− channels reduced beat‐to‐beat AP alternations, but prolonged APD and failed to suppress CaT alternans. In contrast, AP shortening induced by activators of two K+ channels (ML277 for Kv7.1 and NS1643 for Kv11.1) abolished both APD and CaT alternans in field‐stimulated and current‐clamped myocytes. K+ channel activators had no effect on the degree of Ca2+ alternans in AP voltage‐clamped cells, confirming that suppression of Ca2+ alternans was caused by the changes in AP morphology. Finally, activation of Kv11.1 channel significantly attenuated or even abolished atrial T‐wave alternans in isolated Langendorff perfused hearts. In summary, AP shortening suppressed or completely eliminated both CaT and APD alternans in single atrial myocytes and atrial T‐wave alternans at the whole heart level. Therefore, we suggest that AP shortening is a potential intervention to avert development of alternans with important ramifications for arrhythmia prevention and therapy.

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Section: Discussionmentioning

confidence: 97%

Section: Figure 9 K + Channel Agonists Have No Effect On Cat Alternamentioning

confidence: 99%

Action potential shortening rescues atrial calcium alternans

Kanaporis

Kalik

Blatter

2018

The Journal of Physiology

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“…VDACs are transmembrane channels that transport ions and metabolites and play an important regulatory role in ferroptosis 15 . Yagoda et al 4 found that erastin acts on VDACs, leading to mitochondrial dysfunction and resulting in a large amount of released oxides, eventually leading to iron-mediated cell death.…”

Section: Ferroptosis Mediated By Mitochondrial Vdacsmentioning

confidence: 99%

Ferroptosis: past, present and future

et al. 2020

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Ferroptosis is a new type of cell death that was discovered in recent years and is usually accompanied by a large amount of iron accumulation and lipid peroxidation during the cell death process; the occurrence of ferroptosis is iron-dependent. Ferroptosis-inducing factors can directly or indirectly affect glutathione peroxidase through different pathways, resulting in a decrease in antioxidant capacity and accumulation of lipid reactive oxygen species (ROS) in cells, ultimately leading to oxidative cell death. Recent studies have shown that ferroptosis is closely related to the pathophysiological processes of many diseases, such as tumors, nervous system diseases, ischemia-reperfusion injury, kidney injury, and blood diseases. How to intervene in the occurrence and development of related diseases by regulating cell ferroptosis has become a hotspot and focus of etiological research and treatment, but the functional changes and specific molecular mechanisms of ferroptosis still need to be further explored. This paper systematically summarizes the latest progress in ferroptosis research, with a focus on providing references for further understanding of its pathogenesis and for proposing new targets for the treatment of related diseases. Facts Ferroptosis is a new type of programmed cell death, which occurs with iron dependence. Ferroptosis plays an important regulatory role in the occurrence and development of many diseases, such as tumors, neurological diseases, acute kidney injury, ischemia/reperfusion, etc. Activating or blocking the ferroptosis pathway to alleviate the progression of the disease, which provides a promising therapeutic strategy for many diseases. Open questions What is the relationship between ferroptosis and other types of cell death? Is it synergy or antagonism? Is iron necessary to promote the production of lipid peroxides, or can other substances take the place of iron in ferroptosis? What is the downstream regulation mechanism of iron in ferroptosis? How can ferroptosis promote the development of inflammation?

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“…Overall ROS levels were measured by flow cytometry using specific dyes, 2′,7′-dichlorofluorescin diacetate (DCFH-DA; Sigma) for reactive oxygen species (ROS), CellROX Green (Life Technologies) for superoxide anion (•O 2 -), or MitoSOX™ Red (Life Technologies) for mitochondrial superoxide and DAF-FM (Life Technologies) for nitric oxide (NO), as described previously [13, 14]. DCFH-DA, a cell-permeable non-fluorescent probe, converts into the highly fluorescent 2′,7′-dichlorofluorescein (DCF) upon deacetylation by intracellular esterases and oxidation by ROS.…”

Section: Methodsmentioning

confidence: 99%

The adipokine vaspin reduces apoptosis in human hepatocellular carcinoma (Hep-3B) cells, associated with lower levels of NO and superoxide anion

Skonieczna

Hudy

Hejmo

et al. 2019

BMC Pharmacol Toxicol

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Background Among adipose-derived factors, adipocytokines play roles as hormones and signaling mediators for apoptotic pathway. Among of them, vaspin, regulates the metabolism of adipose tissue itself as an endocrine organ, and stimulates adipocytes to maturation, differentiation, etc. Damaged adipocytes, present in obesity and hepatocellular carcinoma (HCC) respond with over-production of inflammatory cytokines. Such pro-inflammatory stimulation remains under adipokine control. Pro-inflammatory pathways are connected to oxidative stress and apoptosis, reported as co-existing with an elevated level of some adipokines in cancer cell lines. However, some hormones, such as vaspin, reduce apoptosis, have anti-inflammatory and anti-oxidative roles in cancer cell lines. Methods Hep-3B cells were cytometrically evaluated under vaspin treatment for reactive oxygen species (ROS) and apoptosiss induction. The statistical significant changes to the untreated controls was calculated by T-tests (indicated at value p < 0.05). Results Here we studied the production of reactive oxygen and nitrogen species in cells of HCC line Hep-3B after vaspin treatment. A decreased level of nitric oxide and superoxide anion 24 h after vaspin addition at 5 ng/ml was correlated with restricted, to the physiological level, apoptosis. A protective role of vaspin was displayed as enhanced cell viability and proliferation, which could be a poor prognostic in liver cancer. Conclusions Apoptosis was suppressed after vaspin treatment, together with low levels of nitric oxide and superoxide anions.

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The Impact of DIDS-Induced Inhibition of Voltage-Dependent Anion Channels (VDAC) on Cellular Response of Lymphoblastoid Cells to Ionizing Radiation

Cited by 42 publications

References 45 publications

Action potential shortening rescues atrial calcium alternans

Action potential shortening rescues atrial calcium alternans

Ferroptosis: past, present and future

The adipokine vaspin reduces apoptosis in human hepatocellular carcinoma (Hep-3B) cells, associated with lower levels of NO and superoxide anion

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