PMID- 15094063
OWN - NLM
STAT- MEDLINE
DCOM- 20040603
LR  - 20131121
IS  - 0014-5793 (Print)
IS  - 0014-5793 (Linking)
VI  - 564
IP  - 1-2
DP  - 2004 Apr 23
TI  - Thapsigargin-stimulated MAP kinase phosphorylation via CRAC channels and PLD 
      activation: inhibitory action of docosahexaenoic acid.
PG  - 177-82
AB  - 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.
FAU - Denys, Anne
AU  - Denys A
AD  - Departement de Physiologie, UPRES Lipides et Nutrition, Universite de Bourgogne, 
      Faculte des Sciences de la Vie, 6 Boulevard Gabriel, 21000 Dijon, France.
FAU - Aires, Virginie
AU  - Aires V
FAU - Hichami, Aziz
AU  - Hichami A
FAU - Khan, Naim Akhtar
AU  - Khan NA
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - FEBS Lett
JT  - FEBS letters
JID - 0155157
RN  - 0 (Diglycerides)
RN  - 0 (Fatty Acids, Unsaturated)
RN  - 0 (Ryanodine Receptor Calcium Release Channel)
RN  - 25167-62-8 (Docosahexaenoic Acids)
RN  - 67526-95-8 (Thapsigargin)
RN  - EC 2.7.11.13 (Protein Kinase C)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 3.1.4.4 (Phospholipase D)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Calcium/metabolism
MH  - Diglycerides/biosynthesis
MH  - Docosahexaenoic Acids/*pharmacology
MH  - Enzyme Activation/drug effects
MH  - Fatty Acids, Unsaturated/pharmacology
MH  - Humans
MH  - Jurkat Cells
MH  - Mitogen-Activated Protein Kinase 1/antagonists & inhibitors/metabolism
MH  - Mitogen-Activated Protein Kinase 3
MH  - Mitogen-Activated Protein Kinases/antagonists & inhibitors/*metabolism
MH  - Phospholipase D/*metabolism
MH  - Phosphorylation/drug effects
MH  - Protein Kinase C/metabolism
MH  - Ryanodine Receptor Calcium Release Channel/*metabolism
MH  - Thapsigargin/*pharmacology
EDAT- 2004/04/20 05:00
MHDA- 2004/06/04 05:00
CRDT- 2004/04/20 05:00
PHST- 2004/01/13 00:00 [received]
PHST- 2004/03/09 00:00 [revised]
PHST- 2004/03/11 00:00 [accepted]
PHST- 2004/04/20 05:00 [pubmed]
PHST- 2004/06/04 05:00 [medline]
PHST- 2004/04/20 05:00 [entrez]
AID - S0014579304003618 [pii]
AID - 10.1016/S0014-5793(04)00361-8 [doi]
PST - ppublish
SO  - FEBS Lett. 2004 Apr 23;564(1-2):177-82. doi: 10.1016/S0014-5793(04)00361-8.