RESUMO
The glucocorticoid-regulated protein annexin A1 is a potent inhibitor of hormone exocytosis in the neuroendocrine system, acting in a paracrine/juxtacrine manner. The signaling mechanism employed by annexin A1 in this process is uncertain, although we have recently presented evidence for a role of the formyl peptide receptor in vivo. We sought to characterize the mechanism of action of annexin A1 on exocytosis using the release of adrenocorticotrophin from the corticotroph-like cell line AtT20 as an in vitro model system. Through the comparison of adrenocorticotrophin release from cells expressing either wild-type annexin A1 or mutant forms, we show a critical involvement of phosphorylation on serine 27 and 45 in the translocation of the protein to the membrane and its inhibitory action on exocytosis. Moreover, we show, for the first time, that annexin A1-dependent inhibition of adrenocorticotrophin release involves the enhancement of actin polymerization to prevent exocytosis via formyl peptide receptor and Rho kinase signaling pathways. This finding has significant implications for the inhibitory actions of annexin A1 on exocytosis in other endocrine and immune contexts.
Assuntos
Hormônio Adrenocorticotrópico/metabolismo , Anexina A1/fisiologia , Exocitose/efeitos dos fármacos , Actinas/efeitos dos fármacos , Actinas/metabolismo , Actinas/ultraestrutura , Animais , Anexina A1/genética , Anexina A1/farmacologia , Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia , Linhagem Celular , Corticotrofos/metabolismo , Hormônio Liberador da Corticotropina/farmacologia , Exocitose/fisiologia , Camundongos , Microscopia Eletrônica , Microscopia de Fluorescência , Fosforilação , Multimerização Proteica/efeitos dos fármacos , Receptores de Formil Peptídeo/fisiologia , Transdução de Sinais/fisiologia , Tiazolidinas/farmacologia , Quinases Associadas a rho/fisiologiaRESUMO
Pyomyoma is a rare, yet potentially fatal complication of uterine leiomyoma. Clinically difficult to diagnose as a result of non-specific symptoms, its presentation is commonly confused with fibroid degeneration. Late diagnosis has severe implications, with the mortality of the condition remaining high. Despite the availability of powerful antibiotics, surgical intervention is frequently required for the curative treatment of the critically ill patient. Here, we report a case of postpartum pyomyoma developing after a complicated antenatal course of placenta praevia resulting in recurrent antepartum haemorrhage, preterm prelabour rupture of membranes and eventual emergency caesarean section for cord prolapse. We highlight the diagnostic difficulty and delay in definitive surgical intervention. Using this case, we have emphasised the importance of strong clinical suspicion when faced with a triad of pain, sepsis without an obvious source and a known diagnosis of leiomyoma to prevent fatalities.