Involvement of p38 MAP kinase-mediated cytochrome c release on sphingosine-1-phosphate (S1P)- and N-monomethyl-S1P-induced cell death of PC12 cells.

d-erythro-Sphingosine-1-phosphate (S1P), a sphingolipid metabolite, affects various neuronal functions including cell fate. S1P appears to have contradictory effects in PC12 cells, a neuronal model cell line; neurite retraction and cell survival/differentiation. In the present study, we examined whether S1P induces cell death in undifferentiated PC12 cells.

Decrease in cytosolic phospholipase A2alpha mRNA levels by reactive oxygen species via MAP kinase pathways in PC12 cells: effects of dopaminergic neurotoxins.

Excess production of reactive oxygen species (ROS), including H2O2, leads to neuronal death in pathological conditions. Although ROS stimulates alpha-type cytosolic phospholipase A2 (cPLA2alpha) activity, their role in cPLA2alpha expression has not been elucidated. We investigated the effect of ROS on cPLA2alpha mRNA levels and signaling pathways in rat pheochromocytoma PC12 cells.

Effects of synthetic sphingosine-1-phosphate analogs on arachidonic acid metabolism and cell death.

Sphingolipid metabolites such as sphingosine regulate cell functions including cell death and arachidonic acid (AA) metabolism. D-erythro-C18-Sphingosine-1-phosphate (D-e-S1P), a sphingolipid metabolite, acts as an intracellular messenger in addition to being an endogenous ligand of some cell surface receptors. The development of S1P analogs may be useful for studying and/or regulating S1P-mediated cellular responses.

Nerve growth factor-induced up-regulation of cytosolic phospholipase A2alpha level in rat PC12 cells.

Nerve growth factor (NGF) regulates various types of gene transcription in neurons. One of the cytosolic phospholipase A(2)s, cPLA(2)alpha, which preferentially cleaves phospholipids at the sn-2 position to arachidonic acid (AA), is involved in neuronal responses including survival. We investigated the effect of NGF on cPLA(2)alpha expression and its signaling pathways in PC12 cells, which differentiate into neuronal-like cells with neurites by NGF treatment.

Expression of adhesion molecules by sphingosine 1-phosphate and histamine in endothelial cells.

We investigated the effects of sphingosine 1-phosphate and histamine on the expression of vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1) and E-selectin, and their signaling pathways in human umbilical vein endothelial cells. Sphingosine 1-phosphate increased the mRNA and protein level of VCAM-1, and the mRNAs of E-selectin and ICAM-1. The effects of sphingosine 1-phosphate were inhibited by the pertussis toxin and the respective inhibitors (10 microM 1-[6-[[(17beta)-3-methoxyestra-1,3,5(10)-trien-17-yl]amino]hexyl]-1H-pyrrole-2,5-dione (U73122) for phosphoinositide-specific phospholipase C; 10 microM 4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl)-1H-imidazole (SB203580) for p38 mitogen-activated protein kinase (MAPK); 1 microM 12-(2-cyanoethyl)-6,7,12,13-tetrahydro-13-methyl-5-oxo-5H-indolo(2,3-a)pyrrolo(3,4-c)-carbazole (Gö6976) for the alpha form of protein kinase C (PKC-alpha)), but not by a PKC-delta inhibitor (1 microM rottlerin).