PMID- 15242752
OWN - NLM
STAT- MEDLINE
DCOM- 20050113
LR  - 20141120
IS  - 0016-6480 (Print)
IS  - 0016-6480 (Linking)
VI  - 138
IP  - 1
DP  - 2004 Aug
TI  - Environmental estrogens can affect the function of mussel hemocytes through rapid 
      modulation of kinase pathways.
PG  - 58-69
AB  - Estrogens and estrogenic chemicals can affect several vertebrate non-reproductive 
      functions, the immune response in particular. We have previously shown that in 
      the hemocytes of the marine mollusc Mytilus the natural estrogen 17beta-estradiol 
      (E(2)) can affect the immune function through rapid tyrosine kinase-mediated 
      signalling pathways converging on phosphorylation of both mitogen activated 
      protein kinases (MAPKs) and signal transducers and activators of transcription 
      (STATs), whose activation plays a key role in the immune response. In this work 
      the effects of synthetic estrogens (such as DES), estrogenic chemicals (such as 
      Bisphenol A, Nonylphenol), and plant estrogens (genistein) on mussel hemocytes 
      were evaluated. The results demonstrate that all the EDCs tested exert in vitro 
      effects similar to those of E(2) on lysosomal membrane stability, although at 
      concentrations 1000 times higher than those of the natural estrogen. When the 
      effects of DES, BPA, and NP on tyrosine kinase-mediated cell signalling were 
      investigated, estrogenic compounds showed distinct effects on the phosphorylation 
      state of MAPK and STAT members. In particular, only DES, like E(2), induced p38 
      MAPK phosphorylation, whereas BPA and NP seem to have opposite effects. Moreover, 
      different EDCs significantly decreased the tyrosine phosphorylation state of 
      STAT3 and STAT5, showing a distinct effect with respect to E(2). Experiments with 
      specific kinase inhibitors showed that activation of p38 MAPK, but also of ERK 
      MAPK and PI3-kinase, plays a key role in mediating the effect of DES. On the 
      other hand, the effects of NP were partly mediated by ERK MAPK activation. 
      BPA-induced lysosomal membrane destabilisation was unaffected by either MAPK or 
      PI3-K inhibitors. However, hemocyte pre-treatment with the PKC inhibitor 
      GF109203X prevented the effects of both BPA and NP, this indicating that kinase 
      pathways other than those involving MAPKs are also responsible for mediating the 
      effects of certain EDCs. Overall, the results support the hypothesis that EDCs 
      may rapidly modulate the function of mussel hemocytes through activation of 
      transduction pathways involving different kinase-mediated cascades. Moreover, the 
      effects of EDCs on the phosphorylation state of transcription factor STATs 
      suggest that these compounds may lead to changes in gene expression secondary to 
      modulation of kinase/phosphatases. Our data address to the importance of 
      investigating full range responses to estrogenic chemicals and may help 
      understanding their basic mechanisms of action in ecologically relevant 
      invertebrate species.
FAU - Canesi, Laura
AU  - Canesi L
AD  - Istituto di Scienze Fisiologiche, Universita di Urbino, "Carlo Bo," Loc. 
      Crocicchia, 61029 Urbino, Italy. canesi@uniurb.it
FAU - Lorusso, Lucia Cecilia
AU  - Lorusso LC
FAU - Ciacci, Caterina
AU  - Ciacci C
FAU - Betti, Michele
AU  - Betti M
FAU - Zampini, Massimiliano
AU  - Zampini M
FAU - Gallo, Gabriella
AU  - Gallo G
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Gen Comp Endocrinol
JT  - General and comparative endocrinology
JID - 0370735
RN  - 0 (Estradiol Congeners)
RN  - 0 (Estrogens, Non-Steroidal)
RN  - EC 2.7.- (Phosphotransferases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Animals
MH  - Bivalvia/*physiology
MH  - Cells, Cultured
MH  - Estradiol Congeners/pharmacology
MH  - Estrogens, Non-Steroidal/*pharmacology
MH  - Hemocytes/drug effects/enzymology/*physiology
MH  - In Vitro Techniques
MH  - Intracellular Membranes/drug effects/metabolism
MH  - Lysosomes/drug effects
MH  - Mitogen-Activated Protein Kinases/metabolism
MH  - Phosphorylation
MH  - Phosphotransferases/*physiology
EDAT- 2004/07/10 05:00
MHDA- 2005/01/14 09:00
CRDT- 2004/07/10 05:00
PHST- 2004/02/26 00:00 [received]
PHST- 2004/04/13 00:00 [revised]
PHST- 2004/05/13 00:00 [accepted]
PHST- 2004/07/10 05:00 [pubmed]
PHST- 2005/01/14 09:00 [medline]
PHST- 2004/07/10 05:00 [entrez]
AID - S0016648004001339 [pii]
AID - 10.1016/j.ygcen.2004.05.004 [doi]
PST - ppublish
SO  - Gen Comp Endocrinol. 2004 Aug;138(1):58-69. doi: 10.1016/j.ygcen.2004.05.004.