PMID- 15642633 OWN - NLM STAT- MEDLINE DCOM- 20050315 LR - 20131121 IS - 0166-445X (Print) IS - 0166-445X (Linking) VI - 71 IP - 1 DP - 2005 Jan 18 TI - 'In vivo' effects of Bisphenol A in Mytilus hemocytes: modulation of kinase-mediated signalling pathways. PG - 73-84 AB - Endocrine disrupting chemicals (EDCs) include a variety of natural and synthetic estrogens, as well as estrogen-mimicking chemicals. We have previously shown that in the hemocytes of the mussel Mytilus galloprovincialis Lam. both natural and environmental estrogens in vitro can rapidly affect the phosphorylation state of components of tyrosine kinase-mediated cell signalling, in particular of mitogen activated protein kinases (MAPKs) and signal transducers and activators of transcription (STAT), that are involved in mediating the hemocyte immune response. These effects were consistent with the hypothesis that 'alternative' modes of estrogen action involving kinase-mediated pathways similar to those described in mammalian systems are also present in invertebrate cells. This possibility was investigated in vivo with Bisphenol A (BPA): mussels were injected with BPA and hemocytes sampled at 6, 12, and 24 h post-injection. The results show that BPA (25 nM nominal concentration in the hemolymph) lead to a significant lysosomal membrane destabilisation at all times post-injection, indicating BPA-induced stress conditions in the hemocytes, whereas lower concentrations were ineffective. BPA induced significant changes in the phosphorylation state of MAPK and STAT members, as evaluated by SDS-PAGE and WB of hemocyte protein extracts with specific antibodies, although to a different degree at different exposure times. In particular, BPA induced a dramatic decrease in phosphorylation of the stress-activated p38 MAPK, whose activation is crucial in mediating the bactericidal activity. Moreover, BPA decreased the phosphorylation of a CREB-like transcription factor (cAMP-responsive element binding protein). The results demonstrate that BPA can affect kinase-mediated cell signalling in mussel hemocytes also in vivo, and suggest that EDCs may affect gene expression in mussel cells through modulation of the activity of transcription factors secondary to cytosolic kinase cascades. Overall, these data address the importance of investigating full range responses to EDCs in ecologically relevant marine invertebrate species. FAU - Canesi, Laura AU - Canesi L AD - Istituto di Scienze Fisiologiche, Universita di Urbino Carlo Bo, Loc. Crocicchia, 61029 Urbino PU, Italy. canesi@uniurb.it FAU - Betti, Michele AU - Betti M FAU - Lorusso, Lucia Cecilia AU - Lorusso LC FAU - Ciacci, Caterina AU - Ciacci C FAU - Gallo, Gabriella AU - Gallo G LA - eng PT - Journal Article DEP - 20041124 PL - Netherlands TA - Aquat Toxicol JT - Aquatic toxicology (Amsterdam, Netherlands) JID - 8500246 RN - 0 (Activating Transcription Factor 1) RN - 0 (Benzhydryl Compounds) RN - 0 (DNA-Binding Proteins) RN - 0 (Estrogens, Non-Steroidal) RN - 0 (Milk Proteins) RN - 0 (Phenols) RN - 0 (STAT3 Transcription Factor) RN - 0 (STAT5 Transcription Factor) RN - 0 (Trans-Activators) RN - 0 (Transcription Factors) RN - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases) RN - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases) RN - MLT3645I99 (bisphenol A) SB - IM MH - Activating Transcription Factor 1 MH - Animals MH - Benzhydryl Compounds MH - Bivalvia/*drug effects/metabolism MH - Blotting, Western MH - DNA-Binding Proteins/metabolism MH - Electrophoresis, Polyacrylamide Gel MH - Estrogens, Non-Steroidal/*toxicity MH - Extracellular Signal-Regulated MAP Kinases/metabolism MH - Hemocytes/drug effects/enzymology/metabolism MH - Lysosomes/drug effects/metabolism MH - MAP Kinase Signaling System/*drug effects MH - Milk Proteins/metabolism MH - Phenols/*toxicity MH - Phosphorylation/drug effects MH - STAT3 Transcription Factor MH - STAT5 Transcription Factor MH - Trans-Activators/metabolism MH - Transcription Factors/metabolism MH - p38 Mitogen-Activated Protein Kinases/metabolism EDAT- 2005/01/12 09:00 MHDA- 2005/03/16 09:00 CRDT- 2005/01/12 09:00 PHST- 2004/05/26 00:00 [received] PHST- 2004/10/13 00:00 [revised] PHST- 2004/10/14 00:00 [accepted] PHST- 2005/01/12 09:00 [pubmed] PHST- 2005/03/16 09:00 [medline] PHST- 2005/01/12 09:00 [entrez] AID - S0166-445X(04)00281-4 [pii] AID - 10.1016/j.aquatox.2004.10.011 [doi] PST - ppublish SO - Aquat Toxicol. 2005 Jan 18;71(1):73-84. doi: 10.1016/j.aquatox.2004.10.011. Epub 2004 Nov 24.