Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.4.3 (phospholipase C)
 18,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The neurotrophic actions of pituitary adenylate cyclase-activating polypeptide (PACAP)-38 and leukemia inhibitory factor (LIF) were investigated in human neuroblastoma SH-SY5Y cells. Effects on differentiation were assessed through monitoring morphological changes and Western blot analysis of the expression of neuronal marker proteins. In contrast to PACAP-38, which induced a 5.5-fold increase in the number of neurite-bearing cells, LIF had no significant effect on cell morphology compared to control cells over the 4-day time course. Cells co-treated with PACAP-38+LIF showed a similar increase in neurite-bearing cells compared to those treated with PACAP-38 alone. Cell morphology was similar for PACAP-38-treated and PACAP-38+LIF-co-treated cells, with the formation of bipolar neuron-like cells with long thin neurites, topped by growth cone-like structures and varicosities. SH-SY5Y cells express tyrosine hydroxylase (TH) but only low levels of the neuronal marker proteins: Bcl-2, GAP-43 and choline acetyltransferase (ChAT). Treatment of cells with PACAP-38 induced the expression of Bcl-2, GAP-43, and ChAT but did not appear to alter the expression of TH. LIF failed to induce the expression of GAP-43 and had little effect on the expression of TH, but did induce the expression of Bcl-2 and upregulated the expression of ChAT. Co-treatment with LIF had no effect on PACAP-38-induced expression of Bcl-2, GAP-43, and ChAT. Cells differentiated for 4 days with PACAP-38 or treated with LIF also displayed increased resistance to hypoxic conditions and to treatment with H2O2 and TNFalpha. The increased resistance to hypoxic conditions for PACAP-differentiated cells was blocked by the p38 MAP kinase inhibitor, SB203580, but not by the MEK1 inhibitor, PD98059. Additionally, cell proliferation assays show that LIF, but not PACAP-38, stimulates proliferation of SH-SY5Y cells, and this observed increase by LIF is not attenuated by co-treatment with PACAP. Further investigation of the intracellular signaling pathways mediating the neurotrophic effects of PACAP on SH-SY5Y cells indicate that neither phospholipase C activation nor Ca2+/calmodulin-dependent kinase II (CAMKII) are involved.
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PMID:Neurotrophic actions of PACAP-38 and LIF on human neuroblastoma SH-SY5Y cells. 1850 35

Cholecystokinin [CCK] is a peptide released as a hormone by the proximal gut in response to the presence of peptones and fatty acid in the gut. Considerable evidence suggests that CCK inhibits feeding behavior and gastric function by acting as a paracrine modulator of vagal afferents in the periphery, especially in the duodenum. CCK is also widely distributed throughout the mammalian brain and appears to function as a neurotransmitter and neuromodulator. More recent studies have suggested that CCK may act directly within the CNS to activate central vagal afferent terminal inputs to the solitary nucleus. We have developed an in vitro calcium imaging method that reveals, for the first time, the direct effects of this peptide on vagal terminals in the solitary nucleus. In vitro imaging reveals that CCK provokes increases in intracellular calcium in vagal afferent terminals as a consequence of a complex interaction between protein kinase A [PKA] and phospholipase C [PLC] transduction mechanisms that open L-type calcium channels and causes endoplasmic reticular [ER] calcium release. The subsequent activation of PKC may be responsible for initiating calcium spiking which is dependent on a TTX-sensitive mechanism. Thus, imaging of the isolated but spatially intact hindbrain slice has allowed a more complete appreciation of the interdependent transduction mechanisms used by CCK to excite identified central vagal afferent fibers and varicosities.
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PMID:Mechanisms of action of CCK to activate central vagal afferent terminals. 1865 18