The BH4 domain of Bcl-2 inhibits ER calcium release and apoptosis by binding the regulatory and coupling domain of the IP3 receptor

Depolarization of skeletal muscle cells by either high external K+ or repetitive extracellular field potential pulses induces calcium release from internal stores. The two components of this release are mediated by either ryanodine receptors or inositol 1,4,5-trisphosphate (IP3) receptors and show differences in kinetics, amplitude, and subcellular localization. We have reported that the transcriptional regulators including ERKs, cAMP/Ca2+-response element binding protein, c- fos, c- jun, and egr-1 are activated by K+-induced depolarization and that their activation requires IP3-dependent calcium release. We presently describe the activation of the nuclear transcription factor NF-κB in response to depolarization by either high K+ (chronic) or electrical pulses (fluctuating). Calcium transients of relative short duration activate an NF-κB reporter gene to an intermediate level, whereas long-lasting calcium increases obtained by prolonged electrical stimulation protocols of various frequencies induce maximal activation of NF-κB. This activation is independent of extracellular calcium, whereas calcium release mediated by either ryanodine or IP3 receptors contribute in all conditions tested. NF-κB activation is mediated by IκBα degradation and p65 translocation to the nucleus. Partial blockade by N-acetyl-l-cysteine, a general antioxidant, suggests the participation of reactive oxygen species. Calcium-dependent signaling pathways such as those linked to calcineurin and PKC also contribute to NF-κB activation by depolarization, as assessed by blockade through pharmacological agents. These results suggest that NF-κB activation in skeletal muscle cells is linked to membrane depolarization and depends on the duration of elevated intracellular calcium. It can be regulated by sequential activation of calcium release mediated by the ryanodine and by IP3 receptors.

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Inositol 1,4,5-trisphosphate–induced Calcium Release Is Necessary for Generating the Entire Light Response of Limulus Ventral Photoreceptors

The Journal of General Physiology ◽

10.1085/jgp.200208778 ◽

2003 ◽

Vol 121 (5) ◽

pp. 441-449 ◽

Cited By ~ 8

Author(s):

Alan Fein

Keyword(s):

Calcium Release ◽

Cyclopiazonic Acid ◽

Light Response ◽

Calcium Stores ◽

Ip3 Receptor ◽

Treatment Results ◽

Light Responses ◽

Calcium Buffer ◽

Pressure Injection ◽

Inositol 1,4,5 Trisphosphate

The experiments reported here were designed to answer the question of whether inositol 1,4,5-trisphosphate (IP3)-induced calcium release is necessary for generating the entire light response of Limulus ventral photoreceptors. For this purpose the membrane-permeable IP3 receptor antagonist 2-aminoethoxydiphenyl borate (2APB) (Maruyama, T., T. Kanaji, S. Nakade, T. Kanno, and K. Mikoshiba. 1997. J. Biochem. (Tokyo). 122:498–505) was used. Previously, 2APB was found to inhibit the light activated current of Limulus ventral photoreceptors and reversibly inhibit both light and IP3 induced calcium release as well as the current activated by pressure injection of calcium into the light sensitive lobe of the photoreceptor (Wang, Y., M. Deshpande, and R. Payne. 2002. Cell Calcium. 32:209). In this study 2APB was found to inhibit the response to a flash of light at all light intensities and to inhibit the entire light response to a step of light, that is, both the initial transient and the steady-state components of the response to a step of light were inhibited. The light response in cells injected with the calcium buffer 1,2-bis(o-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid (BAPTA) was reversibly inhibited by 2APB, indicating that these light responses result from IP3-mediated calcium release giving rise to an increase in Cai. The light response obtained from cells after treatment with 100 μM cyclopiazonic acid (CPA), which acts to empty intracellular calcium stores, was reversibly inhibited by 2APB, indicating that the light response after CPA treatment results from IP3-mediated calcium release and a consequent rise in Cai. Together these findings imply that IP3-induced calcium release is necessary for generating the entire light response of Limulus ventral photoreceptors.

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Aβ and NMDAR activation cause mitochondrial dysfunction involving ER calcium release

Neurobiology of Aging ◽

10.1016/j.neurobiolaging.2014.09.006 ◽

2015 ◽

Vol 36 (2) ◽

pp. 680-692 ◽

Cited By ~ 40

Author(s):

Ildete Luísa Ferreira ◽

Elisabete Ferreiro ◽

Jeannette Schmidt ◽

João M. Cardoso ◽

Cláudia M.F. Pereira ◽

...

Keyword(s):

Mitochondrial Dysfunction ◽

Calcium Release ◽

Nmdar Activation ◽

Er Calcium

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Autocrine motility factor/phosphoglucose isomerase regulates ER stress and cell death through control of ER calcium release

Cell Death and Differentiation ◽

10.1038/cdd.2010.181 ◽

2011 ◽

Vol 18 (6) ◽

pp. 1057-1070 ◽

Cited By ~ 28

Author(s):

M Fu ◽

L Li ◽

T Albrecht ◽

J D Johnson ◽

L D Kojic ◽

...

Keyword(s):

Cell Death ◽

Er Stress ◽

Calcium Release ◽

Phosphoglucose Isomerase ◽

Autocrine Motility Factor ◽

Motility Factor ◽

Er Calcium

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Intracellular sphingosine releases calcium from lysosomes

eLife ◽

10.7554/elife.10616 ◽

2015 ◽

Vol 4 ◽

Cited By ~ 65

Author(s):

Doris Höglinger ◽

Per Haberkant ◽

Auxiliadora Aguilera-Romero ◽

Howard Riezman ◽

Forbes D Porter ◽

...

Keyword(s):

Calcium Release ◽

Pore Channel ◽

Niemann Pick Disease ◽

Late Endosomes ◽

Sphingosine 1 Phosphate ◽

Transcription Factor Eb ◽

Type C ◽

Niemann Pick ◽

Pick Disease ◽

Er Calcium

To elucidate new functions of sphingosine (Sph), we demonstrate that the spontaneous elevation of intracellular Sph levels via caged Sph leads to a significant and transient calcium release from acidic stores that is independent of sphingosine 1-phosphate, extracellular and ER calcium levels. This photo-induced Sph-driven calcium release requires the two-pore channel 1 (TPC1) residing on endosomes and lysosomes. Further, uncaging of Sph leads to the translocation of the autophagy-relevant transcription factor EB (TFEB) to the nucleus specifically after lysosomal calcium release. We confirm that Sph accumulates in late endosomes and lysosomes of cells derived from Niemann-Pick disease type C (NPC) patients and demonstrate a greatly reduced calcium release upon Sph uncaging. We conclude that sphingosine is a positive regulator of calcium release from acidic stores and that understanding the interplay between Sph homeostasis, calcium signaling and autophagy will be crucial in developing new therapies for lipid storage disorders such as NPC.

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Inhalational Anesthetics Induce Cell Damage by Disruption of Intracellular Calcium Homeostasis with Different Potencies

Anesthesiology ◽

10.1097/aln.0b013e31817f5c47 ◽

2008 ◽

Vol 109 (2) ◽

pp. 243-250 ◽

Cited By ~ 100

Author(s):

Hui Yang ◽

Ge Liang ◽

Brian J. Hawkins ◽

Muniswamy Madesh ◽

Andrew Pierwola ◽

...

Keyword(s):

Endoplasmic Reticulum ◽

Calcium Release ◽

Cell Damage ◽

Annexin V ◽

Wild Type ◽

Ip3 Receptors ◽

Ip3 Receptor ◽

Minimal Alveolar Concentration ◽

Inhalational Anesthetics ◽

Excessive Activation

Background The authors hypothesized that inhalational anesthetics induced cell damage by causing abnormal calcium release from the endoplasmic reticulum via excessive activation of inositol 1,4,5-trisphosphate (IP3) receptors, with isoflurane having greater potency than sevoflurane or desflurane. Methods The authors treated DT40 chicken B lymphocytes with total IP3 receptor knockout or their corresponding wild-type control cells with equipotent exposure to isoflurane, sevoflurane, and desflurane. The authors then determined the degree of cell damage by counting the percentage of annexin V- or propidium iodide-positively stained cells or measuring caspase-3 activity. They also studied the changes of calcium concentrations in the endoplasmic reticulum, cytosol, and mitochondria evoked by equipotent concentrations of isoflurane, sevoflurane, and desflurane in both types of DT40 cells. Results Prolonged use of 2 minimal alveolar concentration sevoflurane or desflurane (24 h) induced significant cell damage only in DT40 wild-type and not in IP3 receptor total knockout cells, but with significantly less potency than isoflurane. In accord, all three inhalational anesthetics induced significant decrease of calcium concentrations in the endoplasmic reticulum, accompanied by a subsequent significant increase in the cytosol and mitochondrial calcium concentrations only in DT40 wild-type and not in IP3 receptor total knockout cells. Isoflurane treatment showed significantly greater potency of effect than sevoflurane or desflurane. Conclusion Inhalational anesthetics may induce cell damage by causing abnormal calcium release from the endoplasmic reticulum via excessive activation of IP3 receptors. Isoflurane has greater potency than sevoflurane or desflurane to cause calcium release from the endoplasmic reticulum and to induce cell damage.

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Involvement of c-Fos in signaling grp78 induction following ER calcium release

Oncogene ◽

10.1038/sj.onc.1203994 ◽

2000 ◽

Vol 19 (51) ◽

pp. 5936-5943 ◽

Cited By ~ 16

Author(s):

Huiling He ◽

Karen McColl ◽

Clark W Distelhorst

Keyword(s):

Calcium Release ◽

Er Calcium

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Cellular mechanisms and physiological implications of quantal Ca2+ release in pancreatic acinar cells

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1994.267.6.g1058 ◽

1994 ◽

Vol 267 (6) ◽

pp. G1058-G1066 ◽

Cited By ~ 1

Author(s):

R. E. Rutherford ◽

M. Schoeffield-Payne ◽

S. J. Pandol

Keyword(s):

Calcium Release ◽

Pancreatic Enzyme ◽

Intrinsic Property ◽

Enzyme Secretion ◽

Pancreatic Acinar Cells ◽

Ip3 Receptor ◽

Cellular Mechanisms ◽

Pancreatic Acini ◽

Intracellular Pool ◽

Quantal Release

Previous studies in pancreatic acini demonstrated that submaximal concentrations of agonist release only a portion of Ca2+ from the intracellular pool during the first few seconds of stimulation. Despite continued stimulation, no further release of pool Ca2+ takes place. This process has been termed quantal release. Previous hypotheses have proposed that quantal release results from varying sensitivities of the intracellular pool to inositol 1,4,5-trisphosphate (IP3)-mediated Ca2+ release. The purpose of the present experiments was to further characterize the cellular mechanism of quantal release and to determine the role of quantal release in pancreatic enzyme secretion. The results indicate that the phenomenon of quantal calcium release is not due to varying sensitivities of the intracellular Ca2+ stores to IP3. Quantal release results from both an intrinsic property of the IP3 receptor, which causes it to transport Ca2+ transiently, and from the transient nature of the increase in IP3 generated by submaximal agonist concentration. With this mechanism, sequential additions of physiological concentrations of agonist cause transient increases in intracellular Ca2+ concentration leading to bursts of enzyme secretion.

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NF-κB activated by ER calcium release inhibits Aβ-mediated expression of CHOP protein: Enhancement by AD-linked mutant presenilin 1

Experimental Neurology ◽

10.1016/j.expneurol.2007.04.009 ◽

2007 ◽

Vol 208 (2) ◽

pp. 169-176 ◽

Cited By ~ 22

Author(s):

Jason Schapansky ◽

Kelly Olson ◽

Randy Van Der Ploeg ◽

Gordon Glazner

Keyword(s):

Calcium Release ◽

Presenilin 1 ◽

Er Calcium

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