Mitochondrial potassium channels and reactive oxygen species

Malińska, Dominika; Mirandola, Sandra R.; Kunz, Wolfram S.

doi:10.1016/j.febslet.2010.01.013

Cited by 82 publications

(54 citation statements)

References 55 publications

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“…In particular, mito K ATP , mito BK Ca , and mito Kv1.3 channels have been proposed as potential targets of neuroprotective approaches (14,15). Under pathological conditions, enhanced cytosolic Ca 2ϩ concentrations result in loss of mitochondrial membrane potential (⌬⌿ m ), decreased ATP levels, formation of reactive oxygen species (ROS), and failure of the mitochondrial Ca 2ϩ retention capacity.…”

mentioning

confidence: 99%

Mitochondrial Small Conductance SK2 Channels Prevent Glutamate-induced Oxytosis and Mitochondrial Dysfunction

Dolga

Netter

Perocchi

et al. 2013

Journal of Biological Chemistry

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Background: SK2 channels modulate NMDA-dependent neuronal excitability and provide neuroprotection against excitotoxicity. Results: We identify mito SK2/K Ca 2.2 channels in neuronal mitochondria and demonstrate their protective function in cells lacking NMDAR. Conclusion: SK2 channels prevent mitochondrial dysfunction and completely restore cell viability independently of NMDAR modulation. Significance: Understanding how mitochondrial SK2 channels operate is crucial to develop novel therapeutic strategies for diseases caused by mitochondrial demise.

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confidence: 99%

Mitochondrial Small Conductance SK2 Channels Prevent Glutamate-induced Oxytosis and Mitochondrial Dysfunction

Dolga

Netter

Perocchi

et al. 2013

Journal of Biological Chemistry

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“…It has been reported that a collapse of ΔΨm, resulting from mitoK ATP channel opening, leads to mitochondrial respiratory chain disorders associated with an increase in complex III-dependent ROS and a decrease in complex I-dependent ROS (21). Thus, complex III is considered to be a major ROS-releasing site during phases of decreased membrane potential mediated by mitoK ATP channel opening (28).…”

Section: Discussionmentioning

confidence: 99%

“…ROS has been implicated as a trigger that causes aberrant proliferation or apoptotic resistance in hPASMCs under hypoxic conditions (28). It has been reported that a collapse of ΔΨm, resulting from mitoK ATP channel opening, leads to mitochondrial respiratory chain disorders associated with an increase in complex III-dependent ROS and a decrease in complex I-dependent ROS (21).…”

Section: Discussionmentioning

confidence: 99%

“…As HIF prolyl-hydroxylase utilizes oxygen as a co-substrate, it is inhibited in response to hypoxia, which allows HIF-1α to function. This negative regulation mediated by HIF prolyl-hydroxylase is an additional mechanism of HIF-1α regulation linked to ROS (11,28). Increases in mitochondrial ROS induced by hypoxia has been demonstrated to contribute to HIF-1α stabilization under hypoxic conditions (29)(30)(31).…”

Section: Discussionmentioning

confidence: 99%

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MitoKATP channels promote the proliferation of hypoxic human pulmonary artery smooth muscle cells via the ROS/HIF/miR‑210/ISCU signaling pathway

Ding

Wang

et al. 2017

Exp Ther Med

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Abstract.Previous results have indicated that mitochondrial ATP-sensitive potassium (mitoK ATP ) channels are associated with the hypoxic proliferation of pulmonary artery smooth muscle cells (PASMCs). However, the mechanism underlying the promotive effects of mitoK ATP channels on cell proliferation in response to hypoxia remains unknown. mitoK ATP channel opening results in a collapse of mitochondrial membrane potential and generation of mitochondrial reactive oxygen species (ROS). As hypoxia-inducible factor-1α (HIF-1α) is a critical oxygen sensor and major transcriptional regulator of the hypoxic adaptive response, the current study assessed whether mitoK ATP opening contributes to the chronic proliferation of human PASMCs (hPASMCs) in collaboration with HIF-1α and its downstream targets under hypoxic conditions. The present study demonstrated that there was crosstalk between mitoK ATP channels and HIF-1α signaling in PASMCs under hypoxic conditions. The results suggest that mitoK ATP channels are involved in the proliferation of PASMCs during hypoxia through upregulation of the ROS/HIF/microRNA-210/iron-sulfur cluster protein signaling pathway. IntroductionPulmonary arterial hypertension (PAH) is a life-threatening disorder characterized by obstructive remodeling of the pulmonary arteries, which may lead to right-sided heart failure and mortality (1-2). PAH may be defined as a mean pulmonary artery pressure (mPAP) of ≥20 mmHg at rest or >30 mmHg with exercise, along with a pulmonary artery occlusion pressure of ≤15 mmHg (1-2). The estimated incidence of primary pulmonary hypertension is 1-2/million in the global population (1-2). There are currently three treatment pathways, namely phosphodiesterase type 5 inhibitor or soluble guanylate cyclase stimulator, prostacyclin class therapy and endothelium receptor antagonist, which target the imbalances of three substances; nitric oxide, prostacyclin and endothelin, respectively (3). Despite the efficacy of these pharmacological therapies in improving symptoms, they do not prevent the progression of PAH or reduce the mortality rate of patients (3). Therefore, novel approaches that more effectively target PAH are required to control the cellular components associated with pulmonary remodeling. The chronic and continued proliferation of human pulmonary artery smooth muscle cells (hPASMCs), in addition to apoptotic resistance, leads to hypoxic pulmonary arterial remodeling, which is considered to be a key mechanism for the pathological development of PAH (4). ATP-sensitive potassium (K ATP ) channels are located on the cytoplasmic membrane and on subcellular membranes. Subcellular membrane-associated K ATP channels are divided into three types: Sarcolemmal K ATP , mitochondrial K ATP (mitoK ATP ) and nuclear K ATP . MitoK ATP channels, which contribute to the control of mitochondrial volume and energetic status (5-7), exhibit high sensitivity to hypoxia (8

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“…Kv 1.3 ve benzeri büyük potasyum kanalları, direkt hedefleri olan ve mitokondride bulunan pro-apoptotik özellikteki Bax ve Bad proteinleriyle beraber hücre ölümünde rol oynayabilmektedir [24]. Mitokondrial iç zarda bulunan Kv 1.3 potasyum kanalının inhibisyonu sonucunda da ROS miktarlarının arttığı çeşitli çalışmalarla desteklenmiştir [25][26][27][28]. Kv 1.3 potasyum kanalı kadar periferal kan lenfositlerinde, makrofajlarda, kanser olmayan ve kanser hücre hatlarının mitokondrisinde bulunan Kv 1.3 kanalının eksprese olduğu bildirilmiştir [29].…”

Section: Introductionunclassified

Meme kanserinde Kv 1.3 ve Kv 10.1 voltaj bağımlı potasyum kanallarının inhibisyonunun oksidatif stres üzerindeki rolü

Coşan¹,

Öner²,

Soyocak³

et al. 2017

Dicle Tıp Dergisi

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ÖzetAmaç: Reaktif oksijen türevleri oksidatif stres, iyonize radyasyon maruziyeti, iskemi-reperfüzyon hasarı ve kanseri içeren fizyolojik ve patolojik durumlarda artmaktadır. Çalışmamızda meme kanser hücrelerinin farklılaşmasında ve çoğalmasında etkili olduğu düşünülen voltaj kapılı potasyum kanallarının inhibisyonunun etkilerini gözlemek amaçlandı. Yöntemler: Farklı karakterlerdeki meme kanseri hücrelerine bu potasyum kanallarına özgü siRNA'ların transfeksiyon işlemi yapıldı. İnkübasyon sonrasında hücre lizatları hazırlanarak antioksidan ve oksidan seviyeleri belirlendi. Elde edilen verilerle oksidatif stres hesaplandı. Sürekli değişkenlerin normal dağılıma uygunluğu Kolmogorov-Smirnov testi kullanılarak yapıldı. Normal dağılım gösteren değişkenlerin gruplar arasındaki karşılaştırmaları tek yönlü varyans analizi ile değerlendirildi. Çoklu karşılaştırmalar ise Tukey HSD testi ile gerçekleştirildi. Bulgular: Kanal inhibisyonu ile invaziv olmayan karakterdeki MCF-7 hücrelerinin oksidatif stres seviyesinde düşüş olduğu gözlendi. İnvaziv karakterdeki MDA-MB-231 hücrelerinde ise Kv 1.3 siRNA transfekte edilen grupta oksidatif stres seviyesinde düşüş belirlenirken, Kv 10.1 siRNA transfekte edilen grupta artış belirlendi. Sonuç: Voltaj kapılı potasyum iyon kanallarının inhibisyonunun kanser hücrelerinde oksidatif stres oluşturabileceği belirlenmiştir. Ayrıca, çalışmamızdaki en önemli bulgu kanser hücrelerinde voltaj bağımlı potasyum kanallarının oksidatif stres üzerinde etki yapabileceği ve bunun hücrelerin metastatik karakteri ve iyon kanalı türü ile bağlantılı olmasıdır.

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Mitochondrial potassium channels and reactive oxygen species

Cited by 82 publications

References 55 publications

Mitochondrial Small Conductance SK2 Channels Prevent Glutamate-induced Oxytosis and Mitochondrial Dysfunction

Mitochondrial Small Conductance SK2 Channels Prevent Glutamate-induced Oxytosis and Mitochondrial Dysfunction

MitoKATP channels promote the proliferation of hypoxic human pulmonary artery smooth muscle cells via the ROS/HIF/miR‑210/ISCU signaling pathway

Meme kanserinde Kv 1.3 ve Kv 10.1 voltaj bağımlı potasyum kanallarının inhibisyonunun oksidatif stres üzerindeki rolü

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