RESUMO
Hospice of Sacred Heart, an agency of PeaceHealth Oregon, experienced a dramatic increase in its census beginning in 2007. The spiritual care team noticed the number of referrals was decreasing while the census was increasing. A quality improvement initiative was conducted, including a staff survey, an education program about spirituality and the role of chaplains on interdisciplinary teams in the hospice setting, and an audit of the chaplain's daily allocation of time. These actions resulted in an increase in the use of spiritual care services by patients and staff and the addition of two full-time, benefited chaplain positions.
Assuntos
Pessoal de Saúde/educação , Acessibilidade aos Serviços de Saúde/organização & administração , Cuidados Paliativos na Terminalidade da Vida/organização & administração , Equipe de Assistência ao Paciente/organização & administração , Melhoria de Qualidade/organização & administração , Espiritualidade , Adulto , Cuidadores/educação , Feminino , Seguimentos , Humanos , Comunicação Interdisciplinar , Masculino , Pessoa de Meia-Idade , Avaliação das Necessidades/organização & administração , Oregon , Relações Profissional-Paciente , Apoio Social , Adulto JovemRESUMO
We report the identification and characterization of a novel lipid kinase that phosphorylates multiple substrates. This enzyme, which we term MuLK for multi-substrate lipid kinase, does not belong to a previously described lipid kinase family. MuLK has orthologs in many organisms and is broadly expressed in human tissues. Although predicted to be a soluble protein, MuLK co-fractionates with membranes and localizes to an internal membrane compartment. Recombinant MuLK phosphorylates diacylglycerol, ceramide, and 1-acylglycerol but not sphingosine. Although its affinity for diacylglycerol and ceramide are similar, MuLK exhibits a higher V(max) toward diacylglycerol in vitro, consistent with it acting primarily as a diacylglycerol kinase. MuLK activity was inhibited by sphingosine and enhanced by cardiolipin. It was stimulated by calcium when magnesium concentrations were low and inhibited by calcium when magnesium concentrations were high. The effects of charged lipids and cations on MuLK activity in vitro suggest that its activity in vivo is tightly regulated by cellular conditions.
Assuntos
Lipídeos/química , Fosfotransferases (Aceptor do Grupo Álcool)/química , Fosfotransferases (Aceptor do Grupo Álcool)/genética , Sequência de Aminoácidos , Animais , Encéfalo/metabolismo , Cardiolipinas/química , Cátions , Membrana Celular/metabolismo , DNA Complementar/metabolismo , Diacilglicerol Quinase/química , Diglicerídeos/química , Relação Dose-Resposta a Droga , Biblioteca Gênica , Genoma Humano , Proteínas de Fluorescência Verde , Humanos , Íons , Cinética , Proteínas Luminescentes/metabolismo , Camundongos , Dados de Sequência Molecular , Pâncreas/metabolismo , Fosforilação , Filogenia , Estrutura Terciária de Proteína , RNA Mensageiro/metabolismo , Proteínas Recombinantes/química , Esfingosina/metabolismo , Frações Subcelulares/metabolismo , Distribuição TecidualRESUMO
BACKGROUND: The expression of the rodent phosphoinositide-specific phospholipase C delta-4 (PLCdelta4) has been found to be elevated upon mitogenic stimulation and expression analysis have linked the upregulation of PLCdelta4 expression with rapid proliferation in certain rat transformed cell lines. The human homologue of PLCdelta4 has not been extensively characterized. Accordingly, we investigate the effects of overexpression of human PLCdelta4 on cell signaling and proliferation in this study. RESULTS: The cDNA for human PLCdelta4 has been isolated and expressed ectopically in breast cancer MCF-7 cells. Overexpression of PLCdelta4 selectively activates protein kinase C-phi and upregulates the expression of epidermal growth factor receptors EGFR/erbB1 and HER2/erbB2, leading to constitutive activation of extracellular signal-regulated kinases 1 and 2 (ERK1/2) pathway in MCF-7 cells. MCF-7 cells stably expressing PLCdelta4 demonstrates several phenotypes of transformation, such as rapid proliferation in low serum, formation of colonies in soft agar, and capacity to form densely packed spheroids in low-attachment plates. The growth signaling responses induced by PLCdelta4 are not reversible by siRNA. CONCLUSION: Overexpression or dysregulated expression of PLCdelta4 may initiate oncogenesis in certain tissues through upregulation of ErbB expression and activation of ERK pathway. Since the growth responses induced by PLCdelta4 are not reversible, PLCdelta4 itself is not a suitable drug target, but enzymes in pathways activated by PLCdelta4 are potential therapeutic targets for oncogenic intervention.