Stromal Interaction Molecule 1 rescues store-operated calcium entry and protects NG115-401L cells against cell death induced by endoplasmic reticulum and mitochondrial oxidative stress

2016 ◽  
Vol 97 ◽  
pp. 137-145 ◽  
Author(s):  
Changfeng Zhang ◽  
David W. Thomas
Keyword(s):  
Oxidative Stress ◽  
Endoplasmic Reticulum ◽  
Cell Death ◽  
Calcium Entry ◽  
Mitochondrial Oxidative Stress ◽  
Stromal Interaction Molecule 1 ◽  
Store Operated Calcium Entry

scholarly journals Hyperglycemia Induces Endoplasmic Reticulum Stress in Atrial Cardiomyocytes, and Mitofusin-2 Downregulation Prevents Mitochondrial Dysfunction and Subsequent Cell Death

2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Ming Yuan ◽  
Mengqi Gong ◽  
Zhiwei Zhang ◽  
Lei Meng ◽  
Gary Tse ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Endoplasmic Reticulum ◽  
Cell Death ◽  
Er Stress ◽  
Mitochondrial Dysfunction ◽  
High Glucose ◽  
Atrial Remodeling ◽  
Mitofusin 2 ◽  
Mitochondrial Oxidative Stress ◽  
Atrial Cardiomyocytes

Mitochondrial oxidative stress and dysfunction play an important role of atrial remodeling and atrial fibrillation (AF) in diabetes mellitus. Endoplasmic reticulum (ER) stress has been linked to both physiological and pathological states including diabetes. The aim of this project is to explore the roles of ER stress in hyperglycemia-induced mitochondrial dysfunction and cell death of atrial cardiomyocytes. High glucose upregulated ER stress, mitochondrial oxidative stress, and mitochondria-associated ER membrane (MAM)- enriched proteins (such as glucose-regulated protein 75 (GRP75) and mitofusin-2 (Mfn2)) of primary cardiomyocytes in vitro. Sodium phenylbutyrate (4-PBA) prevented the above changes. Silencing of Mfn2 in HL-1 cells decreased the Ca2+ transfer from ER to mitochondria under ER stress conditions, which were induced by the ER stress agonist, tunicamycin (TM). Electron microscopy data suggested that Mfn2 siRNA significantly disrupted ER-mitochondria tethering in ER stress-injured HL-1 cells. Mfn2 silencing attenuated mitochondrial oxidative stress and Ca2+ overload, increased mitochondrial membrane potential and mitochondrial oxygen consumption, and protected cells from TM-induced apoptosis. In summary, Mfn2 plays an important role in high glucose-induced ER stress in atrial cardiomyocytes, and Mfn2 silencing prevents mitochondrial Ca2+ overload-mediated mitochondrial dysfunction, thereby decreasing ER stress-mediated cardiomyocyte cell death.

scholarly journals Synthesis and Pharmacological Characterization of 2-Aminoethyl Diphenylborinate (2-APB) Derivatives for Inhibition of Store-Operated Calcium Entry (SOCE) in MDA-MB-231 Breast Cancer Cells

2020 ◽  
Vol 21 (16) ◽  
pp. 5604 ◽  
Author(s):  
Achille Schild ◽  
Rajesh Bhardwaj ◽  
Nicolas Wenger ◽  
Dominic Tscherrig ◽  
Palanivel Kandasamy ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Endoplasmic Reticulum ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Structural Changes ◽  
Calcium Entry ◽  
Imaging Plate ◽  
Ip3 Receptors ◽  
Pharmacological Characterization ◽  
Store Operated Calcium Entry

Calcium ions regulate a wide array of physiological functions including cell differentiation, proliferation, muscle contraction, neurotransmission, and fertilization. The endoplasmic reticulum (ER) is the major intracellular Ca2+ store and cellular events that induce ER store depletion (e.g., activation of inositol 1,4,5-triphosphate (IP3) receptors) trigger a refilling process known as store-operated calcium entry (SOCE). It requires the intricate interaction between the Ca2+ sensing stromal interaction molecules (STIM) located in the ER membrane and the channel forming Orai proteins in the plasma membrane (PM). The resulting active STIM/Orai complexes form highly selective Ca2+ channels that facilitate a measurable Ca2+ influx into the cytosol followed by successive refilling of the ER by the sarcoplasmic/endoplasmic reticulum calcium ATPase (SERCA). STIM and Orai have attracted significant therapeutic interest, as enhanced SOCE has been associated with several cancers, and mutations in STIM and Orai have been linked to immunodeficiency, autoimmune, and muscular diseases. 2-Aminoethyl diphenylborinate (2-APB) is a known modulator and depending on its concentration can inhibit or enhance SOCE. We have synthesized several novel derivatives of 2-APB, introducing halogen and other small substituents systematically on each position of one of the phenyl rings. Using a fluorometric imaging plate reader (FLIPR) Tetra-based calcium imaging assay we have studied how these structural changes of 2-APB affect the SOCE modulation activity at different compound concentrations in MDA-MB-231 breast cancer cells. We have discovered 2-APB derivatives that block SOCE at low concentrations, at which 2-APB usually enhances SOCE.

scholarly journals Curcumin enhances cisplatin-induced human laryngeal squamous cancer cell death through activation of TRPM2 channel and mitochondrial oxidative stress

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Sinem Gökçe Kütük ◽  
Gökçen Gökçe ◽  
Mustafa Kütük ◽  
Hacer Esra Gürses Cila ◽  
Mustafa Nazıroğlu
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Tumor Cells ◽  
Protective Role ◽  
Combination Group ◽  
Control Group ◽  
Mitochondrial Oxidative Stress ◽  
Hep2 Cell ◽  
Trpm2 Channel ◽  
Squamous Cancer

AbstractIn this study, laryngeal tumor cells were killed through the production of excessive reactive oxygen species (ROS) and Ca2+ influx by cisplatin (CISP). Nevertheless, a resistance was determined against CISP treatment in the tumor cells. We have investigated the stimulating role of curcumin (CURC) on CISP-induced human laryngeal squamous cancer (Hep2) cell death through TRPM2 channel activation, and its protective role against the adverse effects of CISP in normal kidney (MPK) cells. Hep2 and MPK cells were divided into four groups as control group, CURC group (10μM for 24 hrs), CISP group (25 μM for 24 hrs), and CURC + CISP combination group. CISP-induced decrease of cell viability, cell count, glutathione peroxidase and glutathione level in Hep2 cells were further increased by CURC treatment, but the CISP-induced normal MPK cell death was reduced by the treatment. CISP-induced increase of apoptosis, Ca2+ fluorescence intensity, TRPM2 expression and current densities through the increase of lipid peroxidation, intracellular and mitochondrial oxidative stress were stimulated by CURC treatment. In conclusion, CISP-induced increases in mitochondrial ROS and cell death levels in Hep2 cells were further enhanced through the increase of TRPM2 activation with the effect of CURC treatment. CISP-induced drug resistance in Hep2 cells might be reduced by CURC treatment.

scholarly journals The tethering function of mitofusin2 controls osteoclast differentiation by modulating the Ca2+–NFATc1 axis

2020 ◽  
Vol 295 (19) ◽  
pp. 6629-6640 ◽  
Author(s):  
Anna Ballard ◽  
Rong Zeng ◽  
Allahdad Zarei ◽  
Christine Shao ◽  
Linda Cox ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Bone Mass ◽  
Intracellular Signaling ◽  
Osteoclast Differentiation ◽  
Calcium Entry ◽  
Calcium Handling ◽  
Mitochondrial Network ◽  
Female Mice ◽  
Mitochondrial Functions ◽  
Store Operated Calcium Entry

Dynamic regulation of the mitochondrial network by mitofusins (MFNs) modulates energy production, cell survival, and many intracellular signaling events, including calcium handling. However, the relative importance of specific mitochondrial functions and their dependence on MFNs vary greatly among cell types. Osteoclasts have many mitochondria, and increased mitochondrial biogenesis and oxidative phosphorylation enhance bone resorption, but little is known about the mitochondrial network or MFNs in osteoclasts. Because expression of each MFN isoform increases with osteoclastogenesis, we conditionally deleted MFN1 and MFN2 (double conditional KO (dcKO)) in murine osteoclast precursors, finding that this increased bone mass in young female mice and abolished osteoclast precursor differentiation into mature osteoclasts in vitro. Defective osteoclastogenesis was reversed by overexpression of MFN2 but not MFN1; therefore, we generated mice lacking only MFN2 in osteoclasts. MFN2-deficient female mice had increased bone mass at 1 year and resistance to Receptor Activator of NF-κB Ligand (RANKL)-induced osteolysis at 8 weeks. To explore whether MFN-mediated tethering or mitophagy is important for osteoclastogenesis, we overexpressed MFN2 variants defective in either function in dcKO precursors and found that, although mitophagy was dispensable for differentiation, tethering was required. Because the master osteoclastogenic transcriptional regulator nuclear factor of activated T cells 1 (NFATc1) is calcium-regulated, we assessed calcium release from the endoplasmic reticulum and store-operated calcium entry and found that the latter was blunted in dcKO cells. Restored osteoclast differentiation by expression of intact MFN2 or the mitophagy-defective variant was associated with normalization of store-operated calcium entry and NFATc1 levels, indicating that MFN2 controls mitochondrion–endoplasmic reticulum tethering in osteoclasts.

scholarly journals STIM1 and STIM2 cooperatively regulate mouse neutrophil store-operated calcium entry and cytokine production

Blood ◽  
2017 ◽  
Vol 130 (13) ◽  
pp. 1565-1577 ◽  
Author(s):  
Regina A. Clemens ◽  
Joshua Chong ◽  
Derayvia Grimes ◽  
Yongmei Hu ◽  
Clifford A. Lowell
Keyword(s):  
Oxidative Stress ◽  
Calcium Signaling ◽  
Signaling Pathways ◽  
Cytokine Production ◽  
Calcium Entry ◽  
Specific Role ◽  
Key Points ◽  
Store Operated Calcium Entry ◽  
Cytokine Synthesis

Key Points STIM1 and STIM2 cooperatively regulate neutrophil SOCE. The interaction of oxidative stress and calcium signaling pathways imparts a specific role for STIM2 in neutrophil cytokine synthesis.

Alginate oligosaccharide protects against endoplasmic reticulum- and mitochondrial-mediated apoptotic cell death and oxidative stress

Biomaterials ◽  
2011 ◽  
Vol 32 (23) ◽  
pp. 5438-5458 ◽  
Author(s):  
Solaleh Khoramian Tusi ◽  
Leila Khalaj ◽  
Ghorbangol Ashabi ◽  
Mahmoud Kiaei ◽  
Fariba Khodagholi
Keyword(s):  
Oxidative Stress ◽  
Endoplasmic Reticulum ◽  
Cell Death ◽  
Apoptotic Cell ◽  
Apoptotic Cell Death ◽  
Alginate Oligosaccharide ◽  
And Oxidative Stress

scholarly journals Regulation of store-operated calcium entry during cell division

2012 ◽  
Vol 40 (1) ◽  
pp. 119-123 ◽  
Author(s):  
Jeremy T. Smyth ◽  
James W. Putney
Keyword(s):  
Endoplasmic Reticulum ◽  
Cell Division ◽  
Recent Work ◽  
Calcium Entry ◽  
Store Operated Calcium Entry ◽  
Dividing Cells ◽  
Complex Mechanisms ◽  
Molecular Components ◽  
Ca2 Channels

Store-operate Ca2+ channels gate Ca2+ entry into the cytoplasm in response to the depletion of Ca2+ from endoplasmic reticulum Ca2+ stores. The major molecular components of store-operated Ca2+ entry are STIM (stromal-interacting molecule) 1 (and in some instances STIM2) that serves as the endoplasmic reticulum Ca2+ sensor, and Orai (Orai1, Orai2 and Orai3) which function as pore-forming subunits of the store-operated channel. It has been known for some time that store-operated Ca2+ entry is shut down during cell division. Recent work has revealed complex mechanisms regulating the functions and locations of both STIM1 and Orai1 in dividing cells.

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