Participation of Ca2+/calmodulin during activation of rat neutrophils by polychlorinated biphenyls

Citation
J. Olivero et Pe. Ganey, Participation of Ca2+/calmodulin during activation of rat neutrophils by polychlorinated biphenyls, BIOCH PHARM, 62(8), 2001, pp. 1125-1132
Citations number
67
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Pharmacology & Toxicology
Journal title
BIOCHEMICAL PHARMACOLOGY
ISSN journal
0006-2952 → ACNP
Volume
62
Issue
8
Year of publication
2001
Pages
1125 - 1132
Database
ISI
SICI code
0006-2952(20011015)62:8<1125:POCDAO>2.0.ZU;2-E
Abstract
The effects of Ca2+ and Ca2+/calmodulin on the polychlorinated biphenyl (PC B)-induced activation of phospholipase A(2) (PLA(2)) in rat neutrophils wer e examined. The commercial PCB mixture Aroclor 1242 induced activation of P LA(2) and promoted an increase in the intracellular free calcium concentrat ion ([Ca2+](i)). Bromoenol lactone (BEL), an inhibitor of the Ca2+-independ ent PLA(2) isoform (iPLA(2)) activated by PCBs, did not abrogate the increa se in [Ca2+](i), suggesting that this change in Ca2+ concentration is not d ownstream from the activation of iPLA(2). TMB-8 [8-(N,N-diethylamino)octyl- 3,4,5-trimethoxybenzoate], a blocker of the release of intracellular Ca2+, decreased Aroclor 1242-induced stimulation of PLA(2) with a maximal inhibit ion of 17% at 50 muM. These two results suggest little direct dependence be tween the PCB-induced activation of iPLA(2) and increase in [Ca2+](i). Calm idazolium and W7 [N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide], two chemically distinct calmodulin inhibitors, inhibited Aroclor 1242-induced P LA, activity, whereas trifluoperazine (TFP), another inhibitor of calmoduli n, had no effect at noncytotoxic concentrations. Thus, activation of PLA(2) is dependent, in part, on calmodulin. Furthermore, both TFP and Aroclor 12 42 inhibited neutrophil degranulation stimulated by the bacterial peptide f ormylmethionyl-leucyl-phenylalanine. These results raise the possibility th at some of the effects of PCBs on neutrophil function can be explained by e ffects on Ca2+/calmodulin-dependent processes. (C) 2001 Elsevier Science In c. All rights reserved.