Basiliolides, a class of tetracyclic C19 dilactones from Thapsia garganica, release Ca2+ from the endoplasmic reticulum and regulate the activity of the transcription factors nuclear factor of activated T cells, nuclear factor-kappa B, and activator protein 1 in T lymphocytes
(2006) In Journal of Pharmacology and Experimental Therapeutics 319(1). p.422-430- Abstract
- Calcium concentration within the endoplasmic reticulum ER) plays an essential role in cell physiology. We have investigated the effects of basiliolides, a novel class of C19 dilactones isolated from Thapsia garganica, on Ca2+ mobilization in T cells. Basiliolide A1 induced a rapid mobilization of intracellular Ca2+ in the leukemia T-cell line Jurkat. First, a rapid calcium peak was observed and inhibited by 1,2-bis(2-aminophenoxy) ethane-N,N,N',N'-tetraacetic acid-acetoxymethyl ester. This initial calcium mobilization was followed by a sustained elevation, mediated by the entry of extracellular calcium through store-operated calcium release-activated Ca2+ (CRAC) channels and sensitive to inhibition by EGTA, and by the CRAC channel... (More)
- Calcium concentration within the endoplasmic reticulum ER) plays an essential role in cell physiology. We have investigated the effects of basiliolides, a novel class of C19 dilactones isolated from Thapsia garganica, on Ca2+ mobilization in T cells. Basiliolide A1 induced a rapid mobilization of intracellular Ca2+ in the leukemia T-cell line Jurkat. First, a rapid calcium peak was observed and inhibited by 1,2-bis(2-aminophenoxy) ethane-N,N,N',N'-tetraacetic acid-acetoxymethyl ester. This initial calcium mobilization was followed by a sustained elevation, mediated by the entry of extracellular calcium through store-operated calcium release-activated Ca2+ (CRAC) channels and sensitive to inhibition by EGTA, and by the CRAC channel inhibitor N-{4-[3,5-bis(trifluoromethyl)-1Hpyrazol1-yl] phenyl}-4-methyl-1,2,3-thiadiazole-5-carboxamide (BTP-2). Basiliolide A1 mobilized Ca2+ from ER stores, but in contrast to thapsigargin, it did not induce apoptosis. Basiliolide A1 induced nuclear factor of activated T cells 1 dephosphorylation and activation that was inhibited by BTP-2 and cyclosporine A. In addition, we found that basiliolide A1 alone did not mediate IKB alpha degradation or RelA phosphorylation (ser536), but it synergized with phorbol 12-myristate 13-acetate to induce a complete degradation of the nuclear factor-KB inhibitory protein and to activate the c-Jun NH2-terminal kinase. Moreover, basiliolide A1 regulated both interleukin-2 and tumor necrosis factor-alpha gene expression at the transcriptional level. In basiliolide B, oxidation of one of the two geminal methyls to a carboxymethyl group retained most of the activity of basiliolide A1. In contrast, basiliolide C, where the 15-carbon is oxidized to an acetoxymethine, was much less active. These findings qualify these compounds as new probes to investigate intracellular calcium homeostasis. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/392652
- author
- Navarrete, Carmen ; Sancho, Rocio ; Caballero, Francisco J. ; Pollastro, Federica ; Fiebich, Bernd L. ; Sterner, Olov LU ; Appendino, Giovanni and Munoz, Eduardo
- organization
- publishing date
- 2006
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of Pharmacology and Experimental Therapeutics
- volume
- 319
- issue
- 1
- pages
- 422 - 430
- publisher
- American Society for Pharmacology and Experimental Therapeutics
- external identifiers
-
- pmid:16840645
- wos:000240767800046
- scopus:33749016046
- ISSN
- 1521-0103
- DOI
- 10.1124/jpet.106.108209
- language
- English
- LU publication?
- yes
- additional info
- The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Organic chemistry (S/LTH) (011001240)
- id
- 7afc4c70-796d-43f9-9720-c54d9d920b92 (old id 392652)
- date added to LUP
- 2016-04-01 16:13:21
- date last changed
- 2022-01-28 18:12:10
@article{7afc4c70-796d-43f9-9720-c54d9d920b92,
abstract = {{Calcium concentration within the endoplasmic reticulum ER) plays an essential role in cell physiology. We have investigated the effects of basiliolides, a novel class of C19 dilactones isolated from Thapsia garganica, on Ca2+ mobilization in T cells. Basiliolide A1 induced a rapid mobilization of intracellular Ca2+ in the leukemia T-cell line Jurkat. First, a rapid calcium peak was observed and inhibited by 1,2-bis(2-aminophenoxy) ethane-N,N,N',N'-tetraacetic acid-acetoxymethyl ester. This initial calcium mobilization was followed by a sustained elevation, mediated by the entry of extracellular calcium through store-operated calcium release-activated Ca2+ (CRAC) channels and sensitive to inhibition by EGTA, and by the CRAC channel inhibitor N-{4-[3,5-bis(trifluoromethyl)-1Hpyrazol1-yl] phenyl}-4-methyl-1,2,3-thiadiazole-5-carboxamide (BTP-2). Basiliolide A1 mobilized Ca2+ from ER stores, but in contrast to thapsigargin, it did not induce apoptosis. Basiliolide A1 induced nuclear factor of activated T cells 1 dephosphorylation and activation that was inhibited by BTP-2 and cyclosporine A. In addition, we found that basiliolide A1 alone did not mediate IKB alpha degradation or RelA phosphorylation (ser536), but it synergized with phorbol 12-myristate 13-acetate to induce a complete degradation of the nuclear factor-KB inhibitory protein and to activate the c-Jun NH2-terminal kinase. Moreover, basiliolide A1 regulated both interleukin-2 and tumor necrosis factor-alpha gene expression at the transcriptional level. In basiliolide B, oxidation of one of the two geminal methyls to a carboxymethyl group retained most of the activity of basiliolide A1. In contrast, basiliolide C, where the 15-carbon is oxidized to an acetoxymethine, was much less active. These findings qualify these compounds as new probes to investigate intracellular calcium homeostasis.}},
author = {{Navarrete, Carmen and Sancho, Rocio and Caballero, Francisco J. and Pollastro, Federica and Fiebich, Bernd L. and Sterner, Olov and Appendino, Giovanni and Munoz, Eduardo}},
issn = {{1521-0103}},
language = {{eng}},
number = {{1}},
pages = {{422--430}},
publisher = {{American Society for Pharmacology and Experimental Therapeutics}},
series = {{Journal of Pharmacology and Experimental Therapeutics}},
title = {{Basiliolides, a class of tetracyclic C19 dilactones from Thapsia garganica, release Ca2+ from the endoplasmic reticulum and regulate the activity of the transcription factors nuclear factor of activated T cells, nuclear factor-kappa B, and activator protein 1 in T lymphocytes}},
url = {{http://dx.doi.org/10.1124/jpet.106.108209}},
doi = {{10.1124/jpet.106.108209}},
volume = {{319}},
year = {{2006}},
}