T Cells Deficient in Inositol 1,4,5-Trisphosphate Receptor Are Resistant to Apoptosis

Jayaraman, Thottala; Marks, Andrew R.

doi:10.1128/mcb.17.6.3005

Cited by 246 publications

(164 citation statements)

References 58 publications

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“…83 Also, IP3R-deficient T cells are resistant to apoptosis induction by dexamethasone. 84 Therefore, these findings suggest that calcium release from the ER, via the IP3R, produces cytoplasmic calcium elevation and ER calcium pool depletion that triggers downstream effector pathways of apoptosis.…”

Section: Changes In Calcium and Potassium Homeostasismentioning

confidence: 99%

Recent insights into the mechanism of glucocorticosteroid-induced apoptosis

2002

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Glucocorticosteroid hormones induce apoptosis in lymphocytes. Therefore, glucocorticoids are commonly used as immunosuppressive and chemotherapeutic agents. This review examines many facets of the process by which glucocorticoids induce apoptosis. This process is divided into three stages, an initiation stage that involves glucocorticoid receptor-mediated gene regulation, a decision stage that involves the counterbalancing influence of prosurvival and proapoptotic factors, and the execution stage which involves caspase and endonuclease activation. Many aspects of glucocorticoid-induced apoptosis, such as mitochondrial dysfunction and caspase activation, are important steps in virtually all forms of apoptosis. But the process glucocorticoid-induced apoptosis differs from other forms of apoptosis in terms of initiation at the transcriptional level and involvement of the multicatalytic proteasome and calcium. Moreover, the abundant opportunity for crosstalk between the glucocorticoid receptor and other signaling pathways increases the complexity of glucocorticoid-induced apoptosis and its regulation.

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Section: Changes In Calcium and Potassium Homeostasismentioning

confidence: 99%

Recent insights into the mechanism of glucocorticosteroid-induced apoptosis

2002

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“…Calcium uptake into mitochondria requires IP3 receptor (IP3R) interaction with the voltage-dependent anion selective channel protein 1 (VDAC-1) on the OMM (Rizzuto et al 1998;Szabadkai et al 2006;Hayashi et al 2009). Both deletion of IP3R or ligand induced inhibition of IP3R blocks activities associated with mitochondrial Ca 2þ influx (Rizzuto et al 1993(Rizzuto et al , 1998Khan et al 1996;Jayaraman and Marks 1997). Elegant experiments have shown that Ca 2þ signaling from the ER to the mitochondria was prevented by altering the spacing between the ER and mitochondria by artificially tethering the two membranes too closely (Csordas et al 2006(Csordas et al , 2010.…”

Section: Er and Mitochondriamentioning

confidence: 99%

Endoplasmic Reticulum Structure and Interconnections with Other Organelles

English

Voeltz

2013

Cold Spring Harbor Perspectives in Biology

286

220

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The endoplasmic reticulum (ER) is a large, continuous membrane-bound organelle comprised of functionally and structurally distinct domains including the nuclear envelope, peripheral tubular ER, peripheral cisternae, and numerous membrane contact sites at the plasma membrane, mitochondria, Golgi, endosomes, and peroxisomes. These domains are required for multiple cellular processes, including synthesis of proteins and lipids, calcium level regulation, and exchange of macromolecules with various organelles at ER-membrane contact sites. The ER maintains its unique overall structure regardless of dynamics or transfer at ER-organelle contacts. In this review, we describe the numerous factors that contribute to the structure of the ER.T he endoplasmic reticulum (ER) is a dynamic organelle responsible for many cellular functions, including the synthesis of proteins and lipids, and regulation of intracellular calcium levels. This review focuses on the distinct and complex morphology of the ER. The structure of the ER is complex because of the numerous distinct domains that exist within one continuous membrane bilayer. These domains are shaped by interactions with the cytoskeleton, by proteins that stabilize membrane shape, and by a homotypic fusion machinery that allows the ER membrane to maintain its continuity and identity. The ER also contains domains that contact the plasma membrane (PM) and other organelles including the Golgi, endosomes, mitochondria, lipid droplets, and peroxisomes. ER contact sites with other organelles and the PM are both abundant and dispersed throughout the cytoplasm, suggesting that they too could influence the overall architecture of the ER. As we will discuss here, ER shape and distribution are regulated by many intrinsic and extrinsic forces. ER STRUCTURE AND FORMATION Domains of the ER Are Stabilized by Membrane-Shaping ProteinsThe endoplasmic reticulum (ER) is a large membrane-bound compartment spread throughout the cytoplasm of eukaryotic cells. It is divided into three major morphologies that include the nuclear envelope (NE), peripheral ER cisternae, and an interconnected tubular network

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“…Transfection of IP3R expression constructs restored this capability; however, the identity of the plasma membrane channel activated by elevated inositol triphosphate and the mechanism of IP3R regulation remain under investigation. Additional studies have also implicated IP3R-mediated CCI as a modulator of apoptosis (12)(13)(14). Jayaraman et al showed that transfection of T lymphocytes with IP3R antisense rendered the cells resistant to apoptotic cell death induced by dexamethasone, ionizing radiation, T-cell receptor ligation, and CD95 crosslinking.…”

Section: Introductionmentioning

confidence: 99%

Mitochondrial-Mediated Disregulation of Ca2+ Is a Critical Determinant of Velcade (PS-341/Bortezomib) Cytotoxicity in Myeloma Cell Lines

et al. 2005

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The proteasome inhibitor bortezomib (also known as PS-341/ Velcade) is a dipeptidyl boronic acid that has recently been approved for use in patients with multiple myeloma. Bortezomib inhibits the activity of the 26S proteasome and induces cell death in a variety of tumor cells; however, the mechanism of cytotoxicity is not well understood. In this report, oligonucleotide microarray analysis of the 8226 multiple myeloma cell line showed a predominant induction of gene products associated with the endoplasmic reticulum secretory pathway following short-term, high-dose exposure to bortezomib. Examination of mediators of endoplasmic reticulum stress-induced cell death showed specific activation of caspase 12, as well as of caspases 8, 9, 7, and 3, and cleavage of bid. Treatment of myeloma cells with bortezomib also showed disregulation of intracellular Ca 2+ as a mechanism of caspase activation. Cotreatment with a panel of Ca 2+ -modulating agents identified the mitochondrial uniporter as a critical regulatory factor in bortezomib cytotoxicity. The uniporter inhibitors ruthenium red and Ru360 prevented caspase activation and bid cleavage, and almost entirely inhibited bortezomib-induced cell death, but had no effect on any other chemotherapeutic drug examined. Additional Ca 2+ -modulating agents, including 2-amino-ethoxydiphenylborate, 1,2-bis (o-aminophenoxy) ethane-tretraacetic acid (acetoxymethyl) ester, and dantrolene, did not alter bortezomib cytotoxicity. Analysis of intracellular Ca 2+ showed that the ruthenium-containing compounds inhibited Ca 2+ store loading and abrogated the desensitized capacitative calcium influx associated with bortezomib treatment. These data support the hypothesis that intracellular Ca 2+ disregulation is a critical determinant of bortezomib cytotoxicity. (Cancer Res 2005; 65(9): 3828-36)

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T Cells Deficient in Inositol 1,4,5-Trisphosphate Receptor Are Resistant to Apoptosis

Cited by 246 publications

References 58 publications

Recent insights into the mechanism of glucocorticosteroid-induced apoptosis

Recent insights into the mechanism of glucocorticosteroid-induced apoptosis

Endoplasmic Reticulum Structure and Interconnections with Other Organelles

Mitochondrial-Mediated Disregulation of Ca2+ Is a Critical Determinant of Velcade (PS-341/Bortezomib) Cytotoxicity in Myeloma Cell Lines

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