Coupling to a glioblastoma-directed antibody potentiates antitumor activity of curcumin.

Current therapies for glioblastoma are largely palliative, involving surgical resection followed by chemotherapy and radiation therapy, which yield serious side effects and very rarely produce complete recovery. Curcumin, a food component, blocked brain tumor formation but failed to eliminate established brain tumors in vivo, probably because of its poor bioavailability. In the glioblastoma GL261 cells, it suppressed the tumor-promoting proteins NF-κB, P-Akt1, vascular endothelial growth factor, cyclin D1 and BClXL and triggered cell death.

Atp8a1 deficiency is associated with phosphatidylserine externalization in hippocampus and delayed hippocampus-dependent learning.

The molecule responsible for the enzyme activity plasma membrane (PM) aminophospholipid translocase (APLT), which catalyzes phosphatidylserine (PS) translocation from the outer to the inner leaflet of the plasma membrane, is unknown in mammals. A Caenorhabditis elegans study has shown that ablation of transbilayer amphipath transporter-1 (TAT-1), which is an ortholog of a mammalian P-type ATPase, Atp8a1, causes PS externalization in the germ cells. We demonstrate here that the hippocampal cells of the dentate gyrus, and Cornu Ammonis (CA1, CA3) in mice lacking Atp8a1 exhibit a dramatic increase in PS externalization.

Coupling to a cancer cell-specific antibody potentiates tumoricidal properties of curcumin.

In vitro studies have shown that curcumin, a polyphenol from the culinary component turmeric, has strong anticancer properties. However, there is no consensus on its therapeutic effect in human. Our earlier experiments involving implanted murine melanoma B16F10 cells in the neck or brain of syngeneic C57BL6 mice showed that tail vein injection of curcumin blocks formation of lesions and tumor in these mice.

Erk1/2-dependent phosphorylation of PKCalpha at threonine 638 in hippocampal 5-HT(1A) receptor-mediated signaling.

Stimulation of the serotonin 1A receptor (5-HT(1A)-R) causes activation of extracellular signal-regulated protein kinase (Erk) and protein kinase C alpha (PKCalpha) in both hippocampal HN2-5 cells and cultured hippocampal slices from postnatal day-15 (P15) mice. Our earlier studies demonstrated that PKCalpha is co-immunoprecipitated with Erk and the phosphorylation of PKCalpha in this Erk-PKCalpha complex is dependent on the Erk pathway. Furthermore, the T(638) residue, which must be phosphorylated for the complete activation of PKCalpha, is within an authentic Erk consensus domain (S/TP), and the PKCalpha protein also contains two docking sites for Erk such as KRGRIYL and KRGIIYRDLKL.