Characterization of a putative calcitonin receptor in IMR 32 human neuroblastoma cells

Spampinato, Santi; Falcucci, Barbara; Cacciaguerra, S.; Campana, Gabriele; Murari, G

doi:10.1016/s0304-3940(99)00661-8

Cited by 8 publications

(15 citation statements)

References 13 publications

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“…Consistent with previous reports (66,67), our results show that ADM increases intracellular cAMP levels in SK-N-SH cells, suggesting that the cAMP-PKA signaling pathway is recruited by ADM. Interestingly, ADM tends to increase intracellular cAMP levels 10 min after ADM treatment, and significant increases in cAMP levels occur after 20 min. Because the ADM-induced increases in cAMP occur slightly earlier than the increases in [Ca 2ϩ ] i and NO release, our data suggest that ADM-induced recruitment of the cAMP-PKA signaling pathway precedes and mediates ADM-induced effects on [Ca 2ϩ ] i and NO release.…”

Section: Camp-pka Signaling Pathway Is Required For Adm-induced Incresupporting

confidence: 93%

“…ADM elevates intracellular cAMP levels in various types of cells (1,18), including neural cells (66,67), and the cAMP-PKA signaling pathway has been shown to mediate many of ADM's effects, including cell proliferation and migration (68,69), cell protection (70), and cell regeneration (71). Consistent with previous reports (66,67), our results show that ADM increases intracellular cAMP levels in SK-N-SH cells, suggesting that the cAMP-PKA signaling pathway is recruited by ADM. Interestingly, ADM tends to increase intracellular cAMP levels 10 min after ADM treatment, and significant increases in cAMP levels occur after 20 min.…”

Section: Camp-pka Signaling Pathway Is Required For Adm-induced Incresupporting

confidence: 90%

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Adrenomedullin Stimulates Nitric Oxide Release from SK-N-SH Human Neuroblastoma Cells by Modulating Intracellular Calcium Mobilization

Krukoff

2005

Endocrinology

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We used SK-N-SH human neuroblastoma cells to test the hypothesis that adrenomedullin (ADM), a multifunctional neuropeptide, stimulates nitric oxide (NO) release by modulating intracellular free calcium concentration ([Ca2+]i) in neuron-like cells. We used a nitrite assay to demonstrate that ADM (10 pM to 100 nM) stimulated NO release from the cells, with a maximal response observed with 1 nM at 30 min. This response was blocked by 1 nM ADM(22-52), an ADM receptor antagonist or 2 microM vinyl-L-NIO, a neuronal NO synthase inhibitor. In addition, 5 microM 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid acetoxymethyl ester, an intracellular calcium chelator, eliminated the ADM-induced NO release. Similar results were observed when the cells were incubated in calcium-free medium or when L-type calcium channels were inhibited with 5 microM nifedipine or 10 microM nitrendipine. Depletion of calcium stores in the endoplasmic reticulum (ER) with 1 microM cyclopiazonic acid or 150 nM thapsigargin, or inhibition of ryanodine-sensitive receptors in the ER with 10 microM ryanodine attenuated the ADM-induced NO release. NO responses to ADM were mimicked by 1 mM dibutyryl cAMP, a cAMP analog, and were abrogated by 5 microM H-89, a protein kinase A inhibitor. Furthermore, Fluo-4 fluorescence-activated cell sorter analysis showed that ADM (1 nM) significantly increased [Ca2+]i at 30 min. This response was blocked by nifedipine (5 microM) or H-89 (5 microM) and was reduced by ryanodine (10 microM). These results suggest that ADM stimulates calcium influx through L-type calcium channels and ryanodine-sensitive calcium release from the ER, probably via cAMP-protein kinase A-dependent mechanisms. These elevations in [Ca2+)]i cause activation of neuronal NO synthase and NO release.

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Section: Camp-pka Signaling Pathway Is Required For Adm-induced Incresupporting

confidence: 93%

Section: Camp-pka Signaling Pathway Is Required For Adm-induced Incresupporting

confidence: 90%

Adrenomedullin Stimulates Nitric Oxide Release from SK-N-SH Human Neuroblastoma Cells by Modulating Intracellular Calcium Mobilization

Krukoff

2005

Endocrinology

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“…Thus, baroreflex curves were generated using a pharmacological pressor agent (phenylephrine, PHEN) and a depressor agent (nitroprusside, NP) before and after ADM and/or its antagonist were microinjected into the RVLM of anesthetized rats. Furthermore, since the cyclic adenosine monophosphate (cAMP)‐protein kinase A (PKA) pathway has been shown to mediate ADM's actions in vitro (Drake et al ., 1999; Spampinato et al ., 1999; Xu & Krukoff, 2005), we coinjected a PKA inhibitor (H‐89) with ADM to determine whether PKA is required for ADM's effects on baroreflex activity.…”

Section: Introductionmentioning

confidence: 99%

Adrenomedullin in the rostral ventrolateral medulla inhibits baroreflex control of heart rate: a role for protein kinase A

Krukoff

2006

British J Pharmacology

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1 The rostral ventrolateral medulla (RVLM) is an essential vasomotor center in the brainstem which participates in maintaining resting levels of arterial pressure and for regulating baroreflex activity. We have demonstrated that microinjections of adrenomedullin (ADM), a vasoactive neuropeptide, into the RVLM cause increased resting mean arterial pressure (MAP) and heart rate (HR). However, the effect of ADM on baroreflex function remains unclear. 2 The purposes of the present study were to investigate the effect of ADM in the RVLM on the regulation of baroreflex activity and to identify the underlying mechanisms. Baroreflex curves were generated with intravenous injections of multiple doses of phenylephrine and nitroprusside. The upper and lower plateaus, reflex range, MAP at the midpoint of HR range (MAP 50 ), and gain were evaluated before and after various microinjections were made into the RVLM of urethane-anesthetized rats. 3 Microinjections of ADM decreased the upper plateau, reflex range, and gain, and increased MAP 50 , indicating that ADM in the RVLM impairs baroreflex function. 4 ADM 22-52 , a putative ADM receptor antagonist, significantly increased the baroreflex gain and upper plateau, demonstrating that endogenous ADM tonically inhibits the baroreflex. Coinjections of ADM with ADM blocked the ADM-induced baroreflex responses. 5 ADM's effect was abolished with H-89, a protein kinase A (PKA) inhibitor. 6 Our results show that ADM in the RVLM exerts an inhibitory effect on baroreflex activity via an ADM receptor-mediated mechanism, and that activation of PKA is involved in this event.

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“…Human neuroblastoma IMR-32 cells have many features that resemble human neurons in the central nervous system (21)(22)(23). Importantly, compared with many other human neuronal cell lines, IMR-32 cells have been shown to be able to synthesize a large amount of endogenous APP 751 and APP 695 and secrete a significant amount A␤ 1-42 together with A␤ 1-40 (21)(22)(23). In addition, A␤ secreted by IMR-32 cells can be effectively detected using highly sensitive sandwich ELISAs (21)(22)(23).…”

mentioning

confidence: 99%

“…Importantly, compared with many other human neuronal cell lines, IMR-32 cells have been shown to be able to synthesize a large amount of endogenous APP 751 and APP 695 and secrete a significant amount A␤ 1-42 together with A␤ 1-40 (21)(22)(23). In addition, A␤ secreted by IMR-32 cells can be effectively detected using highly sensitive sandwich ELISAs (21)(22)(23). These findings suggest that IMR-32 cells may provide a unique system to examine the possible role of Par-4 in APP processing.…”

mentioning

confidence: 99%

Prostate Apoptosis Response-4 Enhances Secretion of Amyloid β Peptide 1–42 in Human Neuroblastoma IMR-32 Cells by a Caspase-dependent Pathway

Guo

Xie

Chang

et al. 2001

Journal of Biological Chemistry

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Prostate apoptosis response-4 (Par-4) is a leucine zipper protein that promotes neuronal cell death in Alzheimer's disease (AD). Neuronal degeneration in AD may result from extracellular accumulation of amyloid ␤ peptide (A␤) 1-42. To examine the effect of Par-4 on A␤ secretion and to reconcile amyloid/apoptosis hypotheses of AD, we generated IMR-32 cell lines that overexpress Par-4 and/or its leucine zipper domain. Overexpression of Par-4 did not significantly affect levels of the endogenously expressed ␤ amyloid precursor protein but drastically increased the A␤ 1-42 /A␤ total ratio in the conditioned media about 6 -8 h after trophic factor withdrawal. Time course analysis of caspase activation reveals that Par-4 overexpression exacerbated caspase activation, which is detectable within 2 h after trophic factor withdrawal. Furthermore, inhibition of caspase activity by the broad spectrum caspase inhibitor BDfmk significantly attenuated the Par-4-induced increase in A␤ 1-42 production. In addition, the effects of Par-4 on secretion of A␤ 1-42 were consistently blocked by co-expression of the leucine zipper domain, indicating that the effect of Par-4 on A␤ secretion may require its interaction with other protein(s). These results suggest that Par-4 increases secretion of A␤ 1-42 largely through a caspase-dependent pathway after apoptotic cascades are initiated.Mutations in familial Alzheimer's disease genes, such as ␤-amyloid precursor protein (APP) 1 , presenilin-1, and presenilin-2, have been shown to regulate the processing of APP and result in increased production of the longer form of amyloid ␤ peptide (A␤), A␤ 1-42 (1-5). It is widely accepted that neuronal degeneration in AD is caused by extracellular accumulation of A␤ 1-42. On the other hand, all three familial Alzheimer's disease genes have been shown to regulate neuronal apoptosis, suggesting that dysregulation of apoptotic pathways may play an important role in neuronal degeneration in AD (6 -10). Importantly, abnormal processing of APP and increased production of A␤ may be induced by apoptotic insults (11)(12)(13)(14). Several studies show that APP in neuronal cells can be processed by caspase-6 and -8 and that this processing can be blocked by caspase inhibitors (12, 15).We recently identified Par-4 as a novel cell death-promoting protein associated with neuronal degeneration in AD (16, 17 -42 (18 -20). These data strongly suggest that induction of Par-4 is an important and necessary event in the pathogenic mechanisms of Alzheimer's presenilin-1 mutations and is very likely involved in the abnormal processing of APP during the apoptotic process. To provide better solutions for the treatment of Alzheimer's disease, it is very important to reconcile amyloid/apoptosis hypotheses of AD and examine how Par-4 might alter APP processing during apoptosis, leading to increased production of the neurotoxic A␤ 1-42.The cell types responsible for overproduction of A␤ 1-42 are not completely known, although it has been suggested that A␤ 1-42 is produced by huma...

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Characterization of a putative calcitonin receptor in IMR 32 human neuroblastoma cells

Cited by 8 publications

References 13 publications

Adrenomedullin Stimulates Nitric Oxide Release from SK-N-SH Human Neuroblastoma Cells by Modulating Intracellular Calcium Mobilization

Adrenomedullin Stimulates Nitric Oxide Release from SK-N-SH Human Neuroblastoma Cells by Modulating Intracellular Calcium Mobilization

Adrenomedullin in the rostral ventrolateral medulla inhibits baroreflex control of heart rate: a role for protein kinase A

Prostate Apoptosis Response-4 Enhances Secretion of Amyloid β Peptide 1–42 in Human Neuroblastoma IMR-32 Cells by a Caspase-dependent Pathway

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