Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.12 (PKG)
 2,515 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mucin production and secretion by specialized epithelial cells is a common mechanism used by mammals to protect the underlying mucosae against various injuries (pollutants, pathogens, pH). The expression of mucin genes is cell- and tissue-specific but is submitted to variations during cell differentiation, inflammatory process, and is altered during carcinogenesis. The molecular mechanisms responsible for the control of mucin transcription and expression are beginning to be understood as mucin gene promoters and regulatory regions are characterized. The four gel-forming mucin genes, MUC2-MUC5AC-MUC5B-MUC6, are clustered on the p15 arm of chromosome 11. Common regulatory mechanisms (PKA, PKC, PKG and Ca2+ signaling, Sp1/Sp3) may account for the capability of mucous-secreting cells to express several mucin genes simultaneously. In response to an insult or during carcinogenesis, the normal pattern of expression is altered and results from specific answers of the cell by activating different intracellular signaling pathways. 11p15 mucin genes are regulated at the transcriptional level by pro-inflammatory cytokines (IL-1beta, IL-6, TNF-alpha), pleiotropic cytokines (IL-4, IL-13, IL-9), bacterial exoproduct (LPS), growth factors (EGF, TGF-alpha), lipid mediator (PAF), retinoids and hormones. To date, the only downstream cascade known to activate mucin gene transcription is the Src/Ras/MAPK/pp90rsk cascade, which leads to the activation of the transcription factor NF-kappaB. Mucin gene transcription is also regulated by ATF-1, CREB and RAR-alpha transcription factors. Finally, repression of mucin transcription in cancer cells is under the control of the epigenetic mechanism of methylation. As transcriptional regulation of mucin genes begins to be unraveled, it becomes clear that many signaling pathways are involved. Our understanding of mucin gene transcriptional regulation, which awaits more data (identification of the signaling cascades and active cis-elements within promoters and introns), will most certainly lead to the use of mucin genes as molecular markers in cancer and molecular tools in human gene therapy, and to the synthesis of new therapeutic agents in inflammatory diseases of the epithelium.
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PMID:Transcriptional regulation of the 11p15 mucin genes. Towards new biological tools in human therapy, in inflammatory diseases and cancer? 1157 73

The suicidal death of erythrocytes or eryptosis is characterized by cell shrinkage, membrane blebbing and cell membrane phospholipid scrambling resulting in phosphatidylserine exposure at the cell surface. Eryptosis is stimulated in a wide variety of diseases including sepsis, haemolytic uremic syndrome, malaria, sickle-cell anemia, beta-thalassemia, glucose-6-phosphate dehydrogenase (G6PD)-deficiency, phosphate depletion, iron deficiency and Wilson's disease. Moreover, eryptosis is elicited by osmotic shock, oxidative stress, energy depletion as well as a wide variety of endogenous mediators and xenobiotics. Excessive eryptosis is observed in erythrocytes lacking the cGMP-dependent protein kinase type I (cGKI) or the AMP-activated protein kinase AMPK. Inhibitors of eryptosis include erythropoietin, nitric oxide NO, catecholamines and high concentrations of urea. Eryptosis-triggering diseases and chemicals are partially effective by stimulating the formation of ceramide, which in turn fosters cell membrane scrambling. Accordingly, ceramide-induced eryptosis participates in the pathophysiology of several diseases and contributes to the effects of a large number of xenobiotics. The mechanisms underlying ceramide formation in erythrocytes are, however, still ill defined. In case of osmotic cell shrinkage, ceramide formation is apparently due to activation of phospholipase 2, leading to formation of platelet activating factor PAF and PAF-dependent stimulation of ceramide formation, which possibly involves acid sphingomyelinase. Additional experiments are needed to conclusively define the ceramide-generating enzyme and the ceramide-dependent cellular events eventually leading to suicidal erythrocyte death.
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PMID:Ceramide in suicidal death of erythrocytes. 2050 1