Astrocyte ERK phosphorylation precedes K(+)-induced swelling but follows hypotonicity-induced swelling.

Hypotonicity following water intoxication and/or salt loss leads to mainly astrocytic brain swelling. Astrocytic swelling also occurs following brain trauma or ischemia, together with an increase in extracellular K(+) ([K(+)](o)), stimulating a bumetanide/furosemide/ethacrynic acid-inhibitable cotransporter, NKCC1, that accumulates Na(+) and K(+) together with 2 Cl(-) and osmotically obliged water. Either type of swelling may become fatal and is associated with phosphorylation of extracellular regulated kinases 1 and 2 (ERK(1/2)).

Signaling pathways of isoproterenol-induced ERK1/2 phosphorylation in primary cultures of astrocytes are concentration-dependent.

Stimulation of β-adrenoceptors activates the canonical adenylate cyclase pathway (via G(s) protein) but can also evoke phosphorylation of extracellular-regulated kinases 1 and 2 (ERK(1/2) ) via G(s)/G(i) switching or β-arrestin-mediated recruitment of Src. In primary cultures of mouse astrocytes, activation of the former of these pathways required micromolar concentrations of the β(1)/β(2) -adrenergic agonist isoproterenol, that acted on β(1)-adrenoceptors, whereas the latter was activated already by nanomolar concentrations, acting on β(2) receptors. Protein kinase A activity was required for G(s)/G(i) switching, which was followed by Ca(2+) release from intracellular stores and G(iα)- and metalloproteinase-dependent transactivation of the epidermal growth factor receptor (EGFR; at its Y1173 phophorylation site), via its receptor-tyrosine kinase, β-arrestin 1/2 recruitment, and MAPK/ERK kinase-dependent ERK(1/2) phosphorylation.

Astrocytic transactivation by alpha2A-adrenergic and 5-HT2B serotonergic signaling.

EGF receptor transactivation has been known for more than ten years. It is a signal pathway in which a G-protein-coupled receptor (GPCR) signal leads to release of a growth factor, which in turn activates the EGF receptor-tyrosine kinase in the same or adjacent cells. Astrocytes express a number of GPCRs and play key roles in brain function.

ERK phosphorylation in intact, adult brain by alpha(2)-adrenergic transactivation of EGF receptors.

Our previous work demonstrated dexmedetomidine-activated phosphorylation of extracellular regulated kinases 1 and 2 (ERK(1/2)) in primary cultures of mouse astrocytes and showed that it is evoked by alpha(2)-adrenoceptor-mediated transactivation of epidermal growth factor (EGF) receptors, a known response to activation of G(i/o)- or G(q)-coupled receptors [Li, B., Du, T., Li, H.

Comparative proteomic analysis of an Aspergillus fumigatus mutant deficient in glucosidase I (AfCwh41).

Alpha-glucosidase I regulates trimming of the terminal alpha-1,2-glucose residue in the N-glycan processing pathway, which plays an important role in quality control systems in mammalian cells. Previously, we identified the gene encoding alpha-glucosidase I in the opportunistic human fungal pathogen Aspergillus fumigatus, namely Afcwh41. Deletion of the Afcwh41 gene results in a severe reduction of conidia formation, a temperature-sensitive deficiency of cell wall integrity, and abnormalities of polar growth and septation.

Astrocytic alkalinization by therapeutically relevant lithium concentrations: implications for myo-inositol depletion.

Rationale: One theory for therapeutic effects of the lithium ion (Li+) in bipolar disorder is that myo-inositol, needed for phospholipase C-mediated signaling, is depleted by Li(+)-induced inhibition of inositolphosphate hydrolysis or of myo-inositol uptake, an effect demonstrated in cultured mouse astrocytes at high myo-inositol concentrations. In contrast, myo-inositol uptake is inhibited at low concentrations, reflecting that it occurs both by the high-affinity Na(+)-dependent myo-inositol transporter (SMIT) and the lower-affinity H(+)-dependent inositol transporter (HMIT). Increased intracellular pH (pHi) stimulates SMIT but inhibits HMIT, suggesting that the effect of Li+ could be caused by intracellular alkalinization.

Stimulation by vasopressin of ERK phosphorylation and vector-driven water flux in astrocytes is transactivation-dependent.

Vasopressin acts on astrocytic Gq protein- and phospholipase C-coupled V1 receptors. In mesangial cells, which also express the V1 receptor, it stimulates cell growth by activating mitogen-activated protein kinase (MAP kinase) secondary to transactivation of the epidermal growth factor (EGF) receptor. Transactivation is an intracellular/extracellular process, in which activation of a Gq or a Gi/o protein-coupled receptor leads to metalloproteinase-catalyzed shedding of an EGF receptor agonist, which stimulates EGF receptors on the same cell and/or its neighbor(s).