PS227 Silica Nanoparticles Induces Cardiotoxicity Interfering With CA2+ Handling in Adult Rat Cardiomyocytes

Global Heart ◽  
2016 ◽  
Vol 11 (2) ◽  
pp. e51 ◽  
Author(s):  
C.E. Guerrero-Beltrán ◽  
J. Bernal-Ramírez ◽  
A. García-García ◽  
O. Lozano ◽  
G. Torre-Amione ◽  
...  
Keyword(s):  
Silica Nanoparticles ◽  
Rat Cardiomyocytes ◽  
Adult Rat

scholarly journals Silica nanoparticles induce cardiotoxicity interfering with energetic status and Ca2+ handling in adult rat cardiomyocytes

2017 ◽  
Vol 312 (4) ◽  
pp. H645-H661 ◽  
Author(s):  
Carlos Enrique Guerrero-Beltrán ◽  
Judith Bernal-Ramírez ◽  
Omar Lozano ◽  
Yuriana Oropeza-Almazán ◽  
Elena Cristina Castillo ◽  
...  
Keyword(s):  
Silica Nanoparticles ◽  
Glutathione Depletion ◽  
Energy Status ◽  
Adrenergic Stimulation ◽  
Rat Cardiomyocytes ◽  
Atp Production ◽  
Adult Rat ◽  
Intracellular Ca ◽  
Rat Myocytes ◽  
Potential Risks

Recent evidence has shown that nanoparticles that have been used to improve or create new functional properties for common products may pose potential risks to human health. Silicon dioxide (SiO2) has emerged as a promising therapy vector for the heart. However, its potential toxicity and mechanisms of damage remain poorly understood. This study provides the first exploration of SiO2-induced toxicity in cultured cardiomyocytes exposed to 7- or 670-nm SiO2 particles. We evaluated the mechanism of cell death in isolated adult cardiomyocytes exposed to 24-h incubation. The SiO2 cell membrane association and internalization were analyzed. SiO2 showed a dose-dependent cytotoxic effect with a half-maximal inhibitory concentration for the 7 nm (99.5 ± 12.4 µg/ml) and 670 nm (>1,500 µg/ml) particles, which indicates size-dependent toxicity. We evaluated cardiomyocyte shortening and intracellular Ca2+ handling, which showed impaired contractility and intracellular Ca2+ transient amplitude during β-adrenergic stimulation in SiO2 treatment. The time to 50% Ca2+ decay increased 39%, and the Ca2+ spark frequency and amplitude decreased by 35 and 21%, respectively, which suggest a reduction in sarcoplasmic reticulum Ca2+-ATPase (SERCA) activity. Moreover, SiO2 treatment depolarized the mitochondrial membrane potential and decreased ATP production by 55%. Notable glutathione depletion and H2O2 generation were also observed. These data indicate that SiO2 increases oxidative stress, which leads to mitochondrial dysfunction and low energy status; these underlie reduced SERCA activity, shortened Ca2+ release, and reduced cell shortening. This mechanism of SiO2 cardiotoxicity potentially plays an important role in the pathophysiology mechanism of heart failure, arrhythmias, and sudden death. NEW & NOTEWORTHY Silica particles are used as novel nanotechnology-based vehicles for diagnostics and therapeutics for the heart. However, their potential hazardous effects remain unknown. Here, the cardiotoxicity of silica nanoparticles in rat myocytes has been described for the first time, showing an impairment of mitochondrial function that interfered directly with Ca2+ handling.

scholarly journals IP3R1 regulates Ca2+ transport and pyroptosis through the NLRP3/Caspase-1 pathway in myocardial ischemia/reperfusion injury

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Guixi Mo ◽  
Xin Liu ◽  
Yiyue Zhong ◽  
Jian Mo ◽  
Zhiyi Li ◽  
...  
Keyword(s):  
Myocardial Ischemia ◽  
Ischemia Reperfusion Injury ◽  
Cell Model ◽  
Ischemia Reperfusion ◽  
Inflammatory Factors ◽  
Rat Cardiomyocytes ◽  
Adult Rat ◽  
Caspase 1 ◽  
Intracellular Ca ◽  
Myocardial Ischemia Reperfusion

AbstractIntracellular ion channel inositol 1,4,5-triphosphate receptor (IP3R1) releases Ca2+ from endoplasmic reticulum. The disturbance of IP3R1 is related to several neurodegenerative diseases. This study investigated the mechanism of IP3R1 in myocardial ischemia/reperfusion (MI/R). After MI/R modeling, IP3R1 expression was silenced in myocardium of MI/R rats to explore its role in the concentration of myocardial enzymes, infarct area, Ca2+ level, NLRP3/Caspase-1, and pyroptosis markers and inflammatory factors. The adult rat cardiomyocytes were isolated and cultured to establish hypoxia/reperfusion (H/R) cell model. The expression of IP3R1 was downregulated or ERP44 was overexpressed in H/R-induced cells. Nifedipine D6 was added to H/R-induced cells to block Ca2+ channel or Nigericin was added to activate NLRP3. IP3R1 was highly expressed in myocardium of MI/R rats, and silencing IP3R1 alleviated MI/R injury, reduced Ca2+ overload, inflammation and pyroptosis in MI/R rats, and H/R-induced cells. The binding of ERP44 to IP3R1 inhibited Ca2+ overload, alleviated cardiomyocyte inflammation, and pyroptosis. The increase of intracellular Ca2+ level caused H/R-induced cardiomyocyte pyroptosis through the NLRP3/Caspase-1 pathway. Activation of NLRP3 pathway reversed the protection of IP3R1 inhibition/ERP44 overexpression/Nifedipine D6 on H/R-induced cells. Overall, ERP44 binding to IP3R1 inhibits Ca2+ overload, thus alleviating pyroptosis and MI/R injury.

Ca2 Mobilization in Adult Rat Cardiomyocytes by Angiotensin Type 1 and 2 Receptors

1998 ◽  
Vol 55 (9) ◽  
pp. 1413-1418 ◽  
Author(s):  
Qiming Shao ◽  
Laura Saward ◽  
Peter Zahradka ◽  
Naranjan S Dhalla
Keyword(s):  
Rat Cardiomyocytes ◽  
Adult Rat ◽  
Angiotensin Type

Triiodothyronine restricts myofibrillar growth and enhances beating frequency in cultured adult rat cardiomyocytes

1998 ◽  
Vol 93 (5) ◽  
pp. 391-395 ◽  
Author(s):  
M.C. Schaub ◽  
M.A. Hefti ◽  
B.A. Harder ◽  
H.M. Eppenberger
Keyword(s):  
Rat Cardiomyocytes ◽  
Adult Rat ◽  
Beating Frequency

Arachidonic acid mediates dual effect of TNF-α on Ca2+ transients and contraction of adult rat cardiomyocytes

2002 ◽  
Vol 282 (6) ◽  
pp. C1339-C1347 ◽  
Author(s):  
Aïssata Amadou ◽  
Artur Nawrocki ◽  
Martin Best-Belpomme ◽  
Catherine Pavoine ◽  
Françoise Pecker
Keyword(s):  
Arachidonic Acid ◽  
Cyclooxygenase Inhibitors ◽  
High Dose ◽  
Negative Effects ◽  
Dual Effect ◽  
Rat Cardiomyocytes ◽  
Adult Rat ◽  
Tnf Α ◽  
Biphasic Effect

Tumor necrosis factor (TNF)-α has a biphasic effect on heart contractility and stimulates phospholipase A2 (PLA2) in cardiomyocytes. Because arachidonic acid (AA) exerts a dual effect on intracellular Ca2+ concentration ([Ca2+]i) transients, we investigated the possible role of AA as a mediator of TNF-α on [Ca2+]i transients and contraction with electrically stimulated adult rat cardiac myocytes. At a low concentration (10 ng/ml) TNF-α produced a 40% increase in the amplitude of both [Ca2+]i transients and contraction within 40 min. At a high concentration (50 ng/ml) TNF-α evoked a biphasic effect comprising an initial positive effect peaking at 5 min, followed by a sustained negative effect leading to 50–40% decreases in [Ca2+]i transients and contraction after 30 min. Both the positive and negative effects of TNF-α were reproduced by AA and blocked by arachidonyltrifluoromethyl ketone (AACOCF3), an inhibitor of cytosolic PLA2. Lipoxygenase and cyclooxygenase inhibitors reproduced the high-dose effects of TNF-α and AA. The negative effects of TNF-α and AA were also reproduced by sphingosine and were abrogated by the ceramidase inhibitor n-oleoylethanolamine. These results point out the key role of the cytosolic PLA2/AA pathway in mediating the contractile effects of TNF-α.

scholarly journals Adenoprotection of the heart involves phospholipase C-induced activation and translocation of PKC-ε to RACK2 in adult rat and mouse

2009 ◽  
Vol 297 (2) ◽  
pp. H718-H725 ◽  
Author(s):  
Richard A. Fenton ◽  
Satoshi Komatsu ◽  
Mitsuo Ikebe ◽  
Lynne G. Shea ◽  
James G. Dobson
Keyword(s):  
Confocal Microscopy ◽  
Phospholipase C ◽  
Adrenergic Agonist ◽  
Rat Cardiomyocytes ◽  
Scanning Confocal Microscopy ◽  
Adult Rat ◽  
Sds Page ◽  
T Tubules ◽  
Isolated Rat ◽  
Stimulation Of

Adenosine protects the heart from adrenergic overstimulation. This adenoprotection includes the direct anti-adrenergic action via adenosine A1 receptors (A1R) on the adrenergic signaling pathway. An indirect A1R-induced attenuation of adrenergic responsiveness involves the translocation of PKC-ε to t-tubules and Z-line of cardiomyocytes. We investigated with sarcomere imaging, immunocytochemistry imaging, and coimmunoprecipitation (co-IP) whether A1R activation of PKC-ε induces the kinase translocation to receptor for activated C kinase 2 (RACK2) in isolated rat and mouse hearts and whether phospholipase C (PLC) is involved. Rat cardiomyocytes were treated with the A1R agonist chlorocyclopentyladenosine (CCPA) and exposed to primary PKC-ε and RACK2 antibodies with secondaries conjugated to Cy3 and Cy5 (indodicarbocyanine), respectively. Scanning confocal microscopy showed that CCPA caused PKC-ε to reversibly colocalize with RACK2 within 3 min. Additionally, rat and mouse hearts were perfused and stimulated with CCPA or phenylisopropyladenosine to activate A1R, or with phorbol 12-myristate 13-acetate to activate PKC. RACK2 was immunoprecipitated from heart extracts and resolved with SDS-PAGE. Western blotting showed that CCPA, phenylisopropyladenosine, and phorbol 12-myristate 13-acetate in the rat heart increased the PKC-ε co-IP with RACK2 by 186, 49, and >1,000%, respectively. The A1R antagonist 8-cyclopentyl-1,3-dipropylxanthine prevented the CCPA-induced co-IP with RACK2. In mouse hearts, CCPA increased the co-IP of PKC-ε with RACK2 by 61%. With rat cardiomyocytes, the β-adrenergic agonist isoproterenol increased sarcomere shortening by 177%. CCPA reduced this response by 47%, an action inhibited by the PLC inhibitor U-73122 and 8-cyclopentyl-1,3-dipropylxanthine. In conclusion, A1R stimulation of the heart is associated with PLC-initiated PKC-ε translocation and association with RACK2.

scholarly journals Purinergic stimulation of rat cardiomyocytes induces tyrosine phosphorylation and membrane association of phospholipase Cγ: a major mechanism for InsP3 generation

1996 ◽  
Vol 318 (2) ◽  
pp. 723-728 ◽  
Author(s):  
Michel PUCEAT ◽  
Guy VASSORT
Keyword(s):  
Tyrosine Kinase ◽  
Time Course ◽  
Kinase Inhibitor ◽  
Extracellular Atp ◽  
Rat Cardiomyocytes ◽  
Major Mechanism ◽  
Adult Rat ◽  
Hydrolysis Of ◽  
Purinergic Stimulation ◽  
Stimulation Of

Phospholipase Cγ (PLCγ) expression and activation by a purinergic agonist were investigated in adult rat cardiomyocytes. PLCγ is expressed in isolated cardiomyocytes. Stimulation of cells with extracellular ATP induces a rapid increase in membrane-associated PLCγ immunoreactivity most probably due to redistribution of the lipase from the cytosol to the membrane. The purine triggers a significant phosphorylation on tyrosine residues of a cytosolic pool of PLCγ with a time course that correlates with that of translocation. Extracellular ATP also increases intracellular Ins(1,4,5)P3 content. All these events (translocation and phosphorylation of PLCγ, InsP3 formation) are blocked by genistein, a tyrosine kinase inhibitor. The purinergic effect on both PLCγ translocation and phosphorylation are Ca-sensitive. We thus propose that the purinergic stimulation activates a non-receptor tyrosine kinase that phosphorylates PLCγ in the presence of an increased Ca level and induces PLCγ redistribution to the membrane. There, PLCγ becomes activated leading to the hydrolysis of phosphatidylinositol diphosphate and in turn Ins(1,4,5)P3 formation. This cascade of events may play a significant role in the induction of arrhythmogenesis by purinergic agonists.

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