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Dissociation of the effects of the antitumour ether lipid ET-18-OCH3 on cytosolic calcium and on apoptosis.
Br J Pharmacol. 1997 Aug; 121(7):1364-8.BJ

Abstract

1. We have compared the effects of 1-O-octadecyl-2-O-methyl-sn-glycero-3-phosphocholine (ET-18-OCH3) on the cytosolic free calcium concentration ([Ca2+]i) and on apoptosis in several normal and leukaemia cells, including human polymorphonuclear neutrophils (PMNs), U937 cells, and undifferentiated as well as dimethylsulphoxide-differentiated HL60 cells (uHL60 and dHL60, respectively). 2. ET-18-OCH3 produced apoptosis, as evidenced by DNA degradation into oligonucleosome-size fragments, in U937 and uHL60 cells, but not in dHL60 cells or PMNs. 3. ET-18-OCH3 induced an increase in [Ca2+]i mediated through the platelet-activating factor (PAF) receptor in U937, dHL60 cells and PMNs, as shown by cross-desensitization experiments and by prevention of the [Ca2+]i changes by the PAF antagonist WEB-2170. The EC50 values for the increase in [Ca2+]i induced by PAF and ET-18-OCH3 were 5 x 10(-11) and 2.5 x 10(-7) M, respectively. In uHL60 cells the effect of ET-18-OCH3 on [Ca2+]i was very small and was not affected by WEB-2170. 4. PAF did not produce apoptosis in any of the cell types tested. WEB-2170 did not prevent the apoptosis induced by ET-18-OCH3. 5. The uptake of [3H]-ET-18-OCH3 was much larger in U937 and uHL60 cells than in dHL60 cells and PMNs. 6. Our results indicate that the apoptotic effect of ET-18-OCH3 is not related to the changes in [Ca2+]i, effected by interaction with plasma membrane PAF receptors, but to other actions which are associated with the uptake of this drug into the cells.

Authors+Show Affiliations

Departamento de Bioquímica y Biología Molecular y Fisiología, Instituto de Biología y Genética Molecular (IBGM), Universidad de Valladolid-Consejo Superior de Investigaciones Científicas, Facultad de Medicina, Spain.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

9257915

Citation

Alonso, M T., et al. "Dissociation of the Effects of the Antitumour Ether Lipid ET-18-OCH3 On Cytosolic Calcium and On Apoptosis." British Journal of Pharmacology, vol. 121, no. 7, 1997, pp. 1364-8.
Alonso MT, Gajate C, Mollinedo F, et al. Dissociation of the effects of the antitumour ether lipid ET-18-OCH3 on cytosolic calcium and on apoptosis. Br J Pharmacol. 1997;121(7):1364-8.
Alonso, M. T., Gajate, C., Mollinedo, F., Modolell, M., Alvarez, J., & García-Sancho, J. (1997). Dissociation of the effects of the antitumour ether lipid ET-18-OCH3 on cytosolic calcium and on apoptosis. British Journal of Pharmacology, 121(7), 1364-8.
Alonso MT, et al. Dissociation of the Effects of the Antitumour Ether Lipid ET-18-OCH3 On Cytosolic Calcium and On Apoptosis. Br J Pharmacol. 1997;121(7):1364-8. PubMed PMID: 9257915.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Dissociation of the effects of the antitumour ether lipid ET-18-OCH3 on cytosolic calcium and on apoptosis. AU - Alonso,M T, AU - Gajate,C, AU - Mollinedo,F, AU - Modolell,M, AU - Alvarez,J, AU - García-Sancho,J, PY - 1997/8/1/pubmed PY - 1997/8/1/medline PY - 1997/8/1/entrez SP - 1364 EP - 8 JF - British journal of pharmacology JO - Br J Pharmacol VL - 121 IS - 7 N2 - 1. We have compared the effects of 1-O-octadecyl-2-O-methyl-sn-glycero-3-phosphocholine (ET-18-OCH3) on the cytosolic free calcium concentration ([Ca2+]i) and on apoptosis in several normal and leukaemia cells, including human polymorphonuclear neutrophils (PMNs), U937 cells, and undifferentiated as well as dimethylsulphoxide-differentiated HL60 cells (uHL60 and dHL60, respectively). 2. ET-18-OCH3 produced apoptosis, as evidenced by DNA degradation into oligonucleosome-size fragments, in U937 and uHL60 cells, but not in dHL60 cells or PMNs. 3. ET-18-OCH3 induced an increase in [Ca2+]i mediated through the platelet-activating factor (PAF) receptor in U937, dHL60 cells and PMNs, as shown by cross-desensitization experiments and by prevention of the [Ca2+]i changes by the PAF antagonist WEB-2170. The EC50 values for the increase in [Ca2+]i induced by PAF and ET-18-OCH3 were 5 x 10(-11) and 2.5 x 10(-7) M, respectively. In uHL60 cells the effect of ET-18-OCH3 on [Ca2+]i was very small and was not affected by WEB-2170. 4. PAF did not produce apoptosis in any of the cell types tested. WEB-2170 did not prevent the apoptosis induced by ET-18-OCH3. 5. The uptake of [3H]-ET-18-OCH3 was much larger in U937 and uHL60 cells than in dHL60 cells and PMNs. 6. Our results indicate that the apoptotic effect of ET-18-OCH3 is not related to the changes in [Ca2+]i, effected by interaction with plasma membrane PAF receptors, but to other actions which are associated with the uptake of this drug into the cells. SN - 0007-1188 UR - https://www.unboundmedicine.com/medline/citation/9257915/Dissociation_of_the_effects_of_the_antitumour_ether_lipid_ET_18_OCH3_on_cytosolic_calcium_and_on_apoptosis_ L2 - https://doi.org/10.1038/sj.bjp.0701271 DB - PRIME DP - Unbound Medicine ER -