Thapsigargin-stimulated MAP kinase phosphorylation via CRAC channels and PLD activation: inhibitory action of docosahexaenoic acid.
Fiche publication
Date publication
avril 2004
Journal
FEBS letters
Auteurs
Membres identifiés du Cancéropôle Est :
Pr KAHN Naim, Dr HICHAMI Aziz, Dr AIRES Virginie
Tous les auteurs :
Denys A, Aires V, Hichami A, Khan NA
Lien Pubmed
Résumé
This study was conducted on human Jurkat T-cells to investigate the role of depletion of intracellular Ca(2+) stores in the phosphorylation of two mitogen-activated protein kinases (MAPKs), i.e. extracellular signal-regulated kinase (ERK) 1 and ERK2, and their modulation by a polyunsaturated fatty acid, docosahexaenoic acid (DHA). We observed that thapsigargin (TG) stimulated MAPK activation by store-operated calcium (SOC) influx via opening of calcium release-activated calcium (CRAC) channels as tyrphostin-A9, a CRAC channel blocker, and two SOC influx inhibitors, econazole and SKF-96365, diminished the action of the former. TG-stimulated ERK1/ERK2 phosphorylation was also diminished in buffer containing EGTA, a calcium chelator, further suggesting the implication of calcium influx in MAPK activation in these cells. Moreover, TG stimulated the production of diacylglycerol (DAG) by activating phospholipase D (PLD) as propranolol (PROP) (a PLD inhibitor), but not U73122 (a phospholipase C inhibitor), inhibited TG-evoked DAG production in these cells. DAG production and protein kinase C (PKC) activation were involved upstream of MAPK activation as PROP and GF109203X, a PKC inhibitor, abolished the action of TG on ERK1/ERK2 phosphorylation. Furthermore, DHA seems to act by inhibiting PKC activation as this fatty acid diminished TG- and phorbol 12-myristate 13-acetate-induced ERK1/ERK2 phosphorylation in these cells. Together these results suggest that Ca(2+) influx via CRAC channels is implicated in PLD/PKC/MAPK activation which may be a target of physiological agents such as DHA.
Mots clés
Calcium, metabolism, Diglycerides, biosynthesis, Docosahexaenoic Acids, pharmacology, Enzyme Activation, drug effects, Fatty Acids, Unsaturated, pharmacology, Humans, Jurkat Cells, Mitogen-Activated Protein Kinase 1, antagonists & inhibitors, Mitogen-Activated Protein Kinase 3, Mitogen-Activated Protein Kinases, antagonists & inhibitors, Phospholipase D, metabolism, Phosphorylation, drug effects, Protein Kinase C, metabolism, Ryanodine Receptor Calcium Release Channel, metabolism, Thapsigargin, pharmacology
Référence
FEBS Lett.. 2004 Apr 23;564(1-2):177-82