Nuclear calcium signaling by inositol trisphosphate in GH3 pituitary cells
It has been proposed that nuclear and cytosolic Ca2+ ([Ca2+]N and [Ca2+]C) may be regulated independently. We address here the issue of whether inositol trisphosphate (IP3) can, bypassing changes of [Ca2+]C, produce direct release of Ca2+ into the nucleoplasm. We have used targeted aequorins to selectively measure and compare the changes in [Ca2+]C and [Ca2+]N induced by IP3 in GH3 pituitary cells. Heparin, an IP3 inhibitor that does not permeate the nuclear pores, abolished the [Ca2+]C peaks but inhibited only partly the [Ca2+]N peaks. The permeant inhibitor 2-aminoethoxy-diphenyl-borate (2-APB) blocked both responses. Removal of ATP also inhibited more strongly the [Ca2+]C than [Ca2+]N pe…
Toll-like receptors in neuroinflammation, neurodegeneration, and alcohol-induced brain damage
Toll-like receptors (TLRs) or pattern recognition receptors respond to pathogen-associated molecular patterns (PAMPs) or internal damage-associated molecular patterns (DAMPs). TLRs are integral membrane proteins with both extracellular leucine-rich and cytoplasmic domains that initiate downstream signaling through kinases by activating transcription factors like AP-1 and NF-κB, which lead to the release of various inflammatory cytokines and immune modulators. In the central nervous system, different TLRs are expressed mainly in microglia and astroglial cells, although some TLRs are also expressed in oligodendroglia and neurons. Activation of TLRs triggers signaling cascades by the host as a…