PMID- 16198432
OWN - NLM
STAT- MEDLINE
DCOM- 20060605
LR  - 20121115
IS  - 0166-445X (Print)
IS  - 0166-445X (Linking)
VI  - 75
IP  - 3
DP  - 2005 Nov 10
TI  - Effects of the brominated flame retardant tetrabromobisphenol-A (TBBPA) on cell 
      signaling and function of Mytilus hemocytes: involvement of MAP kinases and 
      protein kinase C.
PG  - 277-87
AB  - Brominated flame retardants (BFRs) are a large group of compounds added to or 
      applied as a treatment to polymeric materials to prevent fires. Tetrabisphenol A 
      (TBBPA) is the most important individual BFR used in industry. Although TBBPA and 
      its derivatives can be found in environmental samples, data are very limited on 
      the presence of this compound in biota. Research on mammals indicates that TBBPA 
      has low toxicity in vivo; however, in vitro TBBPA can act as a cytotoxicant, 
      neurotoxicant, immunotoxicant, thyroid hormone agonist and has a weak estrogenic 
      activity; in particular, the effects of TBBPA have been recently ascribed to its 
      interactions with cellular signaling pathways, in particular with mitogen 
      activated protein kinases (MAPKs). TBBPA has high acute toxicity to aquatic 
      organisms, such as algae, molluscs, crustaceans and fish; however, little is 
      known on the mechanisms of action of this compound in the cells of aquatic 
      species. In this work, we investigated the possible effects and mechanisms of 
      action of TBBPA on the immune cells, the hemocytes, of the marine mussel Mytilus 
      galloprovincialis. The results demonstrate that TBBPA in the low micromolar range 
      induces hemocyte lysosomal membrane destabilization. The effect was reduced or 
      prevented by hemocyte pre-treatment by specific inhibitors of MAPKs and of 
      protein kinase C (PKC). TBBPA stimulated phosphorylation of MAPK members and PKC, 
      as evaluated by electrophoresis and Western blotting with 
      anti-phospho-antibodies, although to a different extent and with distinct 
      time-courses. A rapid (from 5 min) and transient increase in phosphoryation of 
      the stress-activated JNK MAPKs and of PKC was observed, followed by a later 
      increase (at 30-60 min) in phosphorylation of extracellularly regulated MAPKs 
      (ERK2 MAPK) and of the stress-activated p38 MAPK. TBBPA significantly stimulated 
      the hemocyte microbicidal activity towards E. coli, lysosomal enzyme release, 
      phagocytic activity and extracellular superoxide (O2-) production. The results 
      demonstrate that TBBPA in vitro activates the immune function of mussel hemocytes 
      through kinase-mediated cell signaling and that common transduction pathways are 
      involved in mediating the effects of this BFR in mammalian and aquatic 
      invertebrate cells.
FAU - Canesi, Laura
AU  - Canesi L
AD  - Istituto di Scienze Fisiologiche, Universita di Urbino Carlo Bo, Loc. Crocicchia, 
      61029 Urbino (PU), Italy. cansei@uniurb.it
FAU - Lorusso, Lucia Cecilia
AU  - Lorusso LC
FAU - Ciacci, Caterina
AU  - Ciacci C
FAU - Betti, Michele
AU  - Betti M
FAU - Gallo, Gabriella
AU  - Gallo G
LA  - eng
PT  - Comparative Study
PT  - Journal Article
DEP - 20050929
PL  - Netherlands
TA  - Aquat Toxicol
JT  - Aquatic toxicology (Amsterdam, Netherlands)
JID - 8500246
RN  - 0 (Antibodies, Phospho-Specific)
RN  - 0 (Flame Retardants)
RN  - 0 (Polybrominated Biphenyls)
RN  - 11062-77-4 (Superoxides)
RN  - EC 2.7.11.13 (Protein Kinase C)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - FQI02RFC3A (tetrabromobisphenol A)
SB  - IM
MH  - Animals
MH  - Antibodies, Phospho-Specific/pharmacology
MH  - Blotting, Western
MH  - Electrophoresis
MH  - Escherichia coli/immunology
MH  - Flame Retardants/*toxicity
MH  - Hemocytes/*drug effects/immunology
MH  - Lysosomes/*drug effects
MH  - Mitogen-Activated Protein Kinases/antagonists & inhibitors/*metabolism
MH  - Mytilus/*drug effects/enzymology
MH  - Phagocytosis/drug effects
MH  - Phosphorylation
MH  - Polybrominated Biphenyls/*toxicity
MH  - Protein Kinase C/antagonists & inhibitors/*metabolism
MH  - Signal Transduction/*drug effects
MH  - Superoxides/metabolism
EDAT- 2005/10/04 09:00
MHDA- 2006/06/06 09:00
CRDT- 2005/10/04 09:00
PHST- 2005/07/19 00:00 [received]
PHST- 2005/08/25 00:00 [revised]
PHST- 2005/08/27 00:00 [accepted]
PHST- 2005/10/04 09:00 [pubmed]
PHST- 2006/06/06 09:00 [medline]
PHST- 2005/10/04 09:00 [entrez]
AID - S0166-445X(05)00286-9 [pii]
AID - 10.1016/j.aquatox.2005.08.010 [doi]
PST - ppublish
SO  - Aquat Toxicol. 2005 Nov 10;75(3):277-87. doi: 10.1016/j.aquatox.2005.08.010. Epub 
      2005 Sep 29.