scholarly journals Peroxisomes contribute to intracellular calcium dynamics in cardiomyocytes and non-excitable cells

2021 ◽  
Vol 4 (9) ◽  
pp. e202000987
Author(s):  
Yelena Sargsyan ◽  
Uta Bickmeyer ◽  
Christine S Gibhardt ◽  
Katrin Streckfuss-Bömeke ◽  
Ivan Bogeski ◽  
...  
Keyword(s):  
Intracellular Calcium ◽  
Hela Cells ◽  
Calcium Influx ◽  
Induced Pluripotent Stem Cell ◽  
Cytosolic Calcium ◽  
Neonatal Rat ◽  
Calcium Handling ◽  
Calcium Stores ◽  
Calcium Dynamics ◽  
Rat Cardiomyocytes

Peroxisomes communicate with other cellular compartments by transfer of various metabolites. However, whether peroxisomes are sites for calcium handling and exchange has remained contentious. Here we generated sensors for assessment of peroxisomal calcium and applied them for single cell-based calcium imaging in HeLa cells and cardiomyocytes. We found that peroxisomes in HeLa cells take up calcium upon depletion of intracellular calcium stores and upon calcium influx across the plasma membrane. Furthermore, we show that peroxisomes of neonatal rat cardiomyocytes and human induced pluripotent stem cell–derived cardiomyocytes can take up calcium. Our results indicate that peroxisomal and cytosolic calcium signals are tightly interconnected both in HeLa cells and in cardiomyocytes. Cardiac peroxisomes take up calcium on beat-to-beat basis. Hence, peroxisomes may play an important role in shaping cellular calcium dynamics of cardiomyocytes.

scholarly journals Peroxisomes contribute to intracellular calcium dynamics

2020 ◽  
Author(s):  
Yelena Sargsyan ◽  
Uta Bickmeyer ◽  
Katrin Streckfuss-Bömeke ◽  
Ivan Bogeski ◽  
Sven Thoms
Keyword(s):  
Intracellular Calcium ◽  
Hela Cells ◽  
Calcium Influx ◽  
Induced Pluripotent Stem Cell ◽  
Cytosolic Calcium ◽  
Neonatal Rat ◽  
Calcium Handling ◽  
Calcium Stores ◽  
Calcium Dynamics ◽  
Rat Cardiomyocytes

AbstractPeroxisomes communicate with other cellular compartments by transfer of various metabolites. However, whether peroxisomes are sites for calcium handling and exchange has remained contentious. Here we generated sensors for assessment of peroxisomal calcium and applied them for single cell-based calcium imaging in HeLa cells and cardiomyocytes. We found that peroxisomes in HeLa cells take up calcium upon depletion of intracellular calcium stores and upon calcium influx across the plasma membrane. Further, we show that peroxisomes of neonatal rat cardiomyocytes and human induced pluripotent stem cell-derived cardiomyocytes can take up calcium in a controlled manner. Our results indicate that peroxisomal and cytosolic calcium signals are tightly interconnected. Hence, peroxisomes may play an important role in shaping cellular calcium dynamics by serving as buffers or sources of intracellular calcium.

scholarly journals Alterations in mitochondrial function and cytosolic calcium induced by hyperglycemia are restored by mitochondrial transcription factor A in cardiomyocytes

2008 ◽  
Vol 295 (6) ◽  
pp. C1561-C1568 ◽  
Author(s):  
Jorge Suarez ◽  
Yong Hu ◽  
Ayako Makino ◽  
Eduardo Fricovsky ◽  
Hong Wang ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Mitochondrial Dna ◽  
High Glucose ◽  
Cytosolic Calcium ◽  
Neonatal Rat ◽  
Calcium Handling ◽  
Mitochondrial Transcription ◽  
Rat Cardiomyocytes ◽  
Mitochondrial Transcription Factor ◽  
Mitochondrial Transcription Factor A

Mitochondrial transcription factor A (TFAM) is essential for mitochondrial DNA transcription and replication. TFAM transcriptional activity is decreased in diabetic cardiomyopathy; however, the functional implications are unknown. We hypothesized that a reduced TFAM activity may be responsible for some of the alterations caused by hyperglycemia. Therefore, we investigated the effect of TFAM overexpression on hyperglycemia-induced cytosolic calcium handling and mitochondrial abnormalities. Neonatal rat cardiomyocytes were exposed to high glucose (30 mM) for 48 h, and we examined whether TFAM overexpression, by protecting mitochondrial DNA, could reestablish calcium fluxes and mitochondrial alterations toward normal. Our results shown that TFAM overexpression increased to more than twofold mitochondria copy number in cells treated either with normal (5.5 mM) or high glucose. ATP content was reduced by 30% and mitochondrial calcium decreased by 40% after high glucose. TFAM overexpression returned these parameters to even higher than control values. Calcium transients were prolonged by 70% after high glucose, which was associated with diminished sarco(endo)plasmic reticulum Ca2+-ATPase 2a and cytochrome- c oxidase subunit 1 expression. These parameters were returned to control values after TFAM overexpression. High glucose-induced protein oxidation was reduced by TFAM overexpression, indicating a reduction of the high glucose-induced oxidative stress. In addition, we found that TFAM activity can be modulated by O-linked β- N-acetylglucosamine glycosylation. In conclusion, TFAM overexpression protected cell function against the damage induced by high glucose in cardiomyocytes.

Role of cAMP and calcium influx in endothelin-1-induced ANP release in rat cardiomyocytes

1997 ◽  
Vol 273 (5) ◽  
pp. E922-E931 ◽  
Author(s):  
M. C. Rebsamen ◽  
D. J. Church ◽  
D. Morabito ◽  
M. B. Vallotton ◽  
U. Lang
Keyword(s):  
Calcium Influx ◽  
Cytosolic Calcium ◽  
Neonatal Rat ◽  
Rat Cardiomyocytes ◽  
Endothelin 1 ◽  
Kinase C ◽  
Ventricular Cardiomyocytes ◽  
Camp Formation ◽  
Prostacyclin Production

The mechanism of endothelin-1 (ET-1)-induced atrial natriuretic peptide (ANP) release was studied in neonatal rat ventricular cardiomyocytes. These cells expressed a single high-affinity class of ETAreceptor (dissociation constant = 54 ± 18 pM, n = 3), but no ETB receptors. Incubation of cardiomyocytes with ET-1 led to concentration-dependent ANP release and prostacyclin production. ET-1-induced ANP release was affected by neither protein kinase C (PKC) inhibition or downregulation nor by cyclooxygenase inhibition, indicating that ET-1-stimulated ANP secretion is not a PKC-mediated, prostaglandin-dependent process. Furthermore, ET-1 significantly stimulated adenosine 3′,5′-cyclic monophosphate (cAMP) production and increased cytosolic calcium concentration in these preparations. Both ET-1-induced calcium influx and ANP release were decreased by the cAMP antagonist Rp-cAMPS, the Rp diastereoisomer of cAMP. Moreover, ET-1-induced ANP secretion was strongly inhibited in the presence of nifedipine as well as in the absence of extracellular calcium. Thus our results suggest that ET-1 stimulates ANP release in ventricular cardiomyocytes via an ETAreceptor-mediated pathway involving cAMP formation and activation of a nifedipine-sensitive calcium channel.

scholarly journals Phosphorylation of NMDA receptors by cyclin B/CDK1 modulates calcium dynamics and mitosis

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Margarita Jacaranda Rosendo-Pineda ◽  
Juan Jesus Vicente ◽  
Oscar Vivas ◽  
Jonathan Pacheco ◽  
Arlet Loza-Huerta ◽  
...  
Keyword(s):  
Calcium Influx ◽  
Cytosolic Calcium ◽  
Calcium Entry ◽  
Cyclin B ◽  
Hek293 Cells ◽  
Cycle Phase ◽  
Calcium Dynamics ◽  
Intracellular Loop ◽  
Pericentriolar Material

AbstractN-methyl-D-aspartate receptors (NMDAR) are glutamate-gated calcium channels named after their artificial agonist. NMDAR are implicated in cell proliferation under normal and pathophysiological conditions. However, the role of NMDAR during mitosis has not yet been explored in individual cells. We found that neurotransmitter-evoked calcium entry via endogenous NMDAR in cortical astrocytes was transient during mitosis. The same occurred in HEK293 cells transfected with the NR1/NR2A subunits of NMDAR. This transient calcium entry during mitosis was due to phosphorylation of the first intracellular loop of NMDAR (S584 of NR1 and S580 of NR2A) by cyclin B/CDK1. Expression of phosphomimetic mutants resulted in transient calcium influx and enhanced NMDAR inactivation independent of the cell cycle phase. Phosphomimetic mutants increased entry of calcium in interphase and generated several alterations during mitosis: increased mitotic index, increased number of cells with lagging chromosomes and fragmentation of pericentriolar material. In summary, by controlling cytosolic calcium, NMDAR modulate mitosis and probably cell differentiation/proliferation. Our results suggest that phosphorylation of NMDAR by cyclin B/CDK1 during mitosis is required to preserve mitotic fidelity. Altering the modulation of the NMDAR by cyclin B/CDK1 may conduct to aneuploidy and cancer.

Cytosolic free Calcium and Intracellular Calcium Stores in Neutrophils from Hypertensive Subjects

1985 ◽  
Vol 69 (2) ◽  
pp. 227-230 ◽  
Author(s):  
P. Daniel Lew ◽  
Laurent Favre ◽  
Francis A. Waldvogel ◽  
Michel B. Vallotton
Keyword(s):  
Essential Hypertension ◽  
Intracellular Calcium ◽  
Calcium Ionophore ◽  
Calcium Handling ◽  
Free Calcium ◽  
Calcium Stores ◽  
Cytosolic Free Calcium ◽  
Intact Cells ◽  
Intracellular Calcium Stores ◽  
Calcium Indicator

1. Alterations in intracellular calcium have been implicated in the pathogenesis of essential hypertension. To see whether this is a generalized phenomenon we assessed cytosolic free calcium and intracellular calcium stores in neutrophils from normo- and hyper-tensive subjects, by trapping the fluorescent calcium indicator quin2 in intact cells. 2. Ten patients with untreated essential hypertension were compared with 10 age- and sex-matched normotensive subjects. The levels of cytosolic free calcium and intracellular calcium stores releasable by the calcium ionophore ionomycin did not differ. No significant relationship was found between blood pressure and the calcium parameters in all 20 subjects studied. 3. The results indicate that essential hypertension is not associated with a membrane defect in calcium handling of all human cell systems, leading to generalized increases in resting values of cytosolic free calcium. 4. Neutrophils do not appear to be a good model for intracellular calcium handling in vascular smooth muscle.

scholarly journals Elucidation of a TRPC6-TRPC5 Channel Cascade That Restricts Endothelial Cell Movement

2008 ◽  
Vol 19 (8) ◽  
pp. 3203-3211 ◽  
Author(s):  
Pinaki Chaudhuri ◽  
Scott M. Colles ◽  
Manjunatha Bhat ◽  
David R. Van Wagoner ◽  
Lutz Birnbaumer ◽  
...  
Keyword(s):  
Intracellular Calcium ◽  
Calcium Concentration ◽  
Transient Receptor Potential ◽  
Calcium Influx ◽  
Cell Movement ◽  
Receptor Potential ◽  
Receptor Activation ◽  
Calcium Stores ◽  
Trpc Channels ◽  
Transient Receptor

Canonical transient receptor potential (TRPC) channels are opened by classical signal transduction events initiated by receptor activation or depletion of intracellular calcium stores. Here, we report a novel mechanism for opening TRPC channels in which TRPC6 activation initiates a cascade resulting in TRPC5 translocation. When endothelial cells (ECs) are incubated in lysophosphatidylcholine (lysoPC), rapid translocation of TRPC6 initiates calcium influx that results in externalization of TRPC5. Activation of this TRPC6–5 cascade causes a prolonged increase in intracellular calcium concentration ([Ca2+]i) that inhibits EC movement. When TRPC5 is down-regulated with siRNA, the lysoPC-induced rise in [Ca2+]i is shortened and the inhibition of EC migration is lessened. When TRPC6 is down-regulated or EC from TRPC6−/− mice are studied, lysoPC has minimal effect on [Ca2+]i and EC migration. In addition, TRPC5 is not externalized in response to lysoPC, supporting the dependence of TRPC5 translocation on the opening of TRPC6 channels. Activation of this novel TRPC channel cascade by lysoPC, resulting in the inhibition of EC migration, could adversely impact on EC healing in atherosclerotic arteries where lysoPC is abundant.

scholarly journals Air bubble contact with endothelial cells in vitro induces calcium influx and IP3-dependent release of calcium stores

2011 ◽  
Vol 301 (3) ◽  
pp. C679-C686 ◽  
Author(s):  
Peter Sobolewski ◽  
Judith Kandel ◽  
Alexandra L. Klinger ◽  
David M. Eckmann
Keyword(s):  
Endothelial Cells ◽  
Intracellular Calcium ◽  
Calcium Release ◽  
Transient Receptor Potential ◽  
Calcium Influx ◽  
Calcium Transient ◽  
Epifluorescence Microscopy ◽  
Transient Receptor Potential Vanilloid ◽  
Calcium Stores ◽  
Air Bubble

Gas embolism is a serious complication of decompression events and clinical procedures, but the mechanism of resulting injury remains unclear. Previous work has demonstrated that contact between air microbubbles and endothelial cells causes a rapid intracellular calcium transient and can lead to cell death. Here we examined the mechanism responsible for the calcium rise. Single air microbubbles (50–150 μm), trapped at the tip of a micropipette, were micromanipulated into contact with individual human umbilical vein endothelial cells (HUVECs) loaded with Fluo-4 (a fluorescent calcium indicator). Changes in intracellular calcium were then recorded via epifluorescence microscopy. First, we confirmed that HUVECs rapidly respond to air bubble contact with a calcium transient. Next, we examined the involvement of extracellular calcium influx by conducting experiments in low calcium buffer, which markedly attenuated the response, or by pretreating cells with stretch-activated channel blockers (gadolinium chloride or ruthenium red), which abolished the response. Finally, we tested the role of intracellular calcium release by pretreating cells with an inositol 1,4,5-trisphosphate (IP3) receptor blocker (xestospongin C) or phospholipase C inhibitor (neomycin sulfate), which eliminated the response in 64% and 67% of cases, respectively. Collectively, our results lead us to conclude that air bubble contact with endothelial cells causes an influx of calcium through a stretch-activated channel, such as a transient receptor potential vanilloid family member, triggering the release of calcium from intracellular stores via the IP3 pathway.

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