Inhibition of AMPK through Lyn-Syk-Akt enhances FcεRI signal pathways for allergic response.

UNLABELLED: AMPK was shown to negatively regulate FcεRI activation, and FcεR-mediated Fyn activation can counteract the LKB1/AMPK axis in mast cells. However, the relationship between the major Src family kinase Lyn and AMPK remains poorly defined. Here, we investigate the molecular mechanism for AMPK inhibition by FcεRI-Lyn signaling in rat RBL-2H3 cells. We found that FcεRI activation could rapidly inhibit AMPK activation through increased AMPK phosphorylation at the inhibitory Ser485/491 residues without a change at the activating Th172 residue, and this was accompanied by a reduction of ACC phosphorylation. Using specific inhibitors and gene silencing, we found that such AMPK inhibition involved a signaling cascade through Lyn-Syk-Akt. When AMPK was activated by AICAR, A769662 and metformin, FcεRI-mediated Syk, ERK, JNK and p38 activation, and TNFα release were all inhibited. Consistently, AMPK inhibition by compound C increased FcεRI-mediated Lyn activation. Moreover, AMPK activation dominantly impaired IgE-induced recruitment of signal proteins to the FcεRI by blocking the formation of FcεRIß-Lyn-Syk, FcεRIγ-Lyn-Syk, and AMPK-FcεRIß complexes. In vitro kinase assay further revealed the ability of AMPKα2 to phosphorylate FcεRIß in the complex. In vivo, AMPK activation by metformin could readily reduce vascular permeability and ear swelling in a mouse model of passive cutaneous anaphylaxis mediated by IgE. In summary, our findings demonstrate that IgE-mediated FcεRI activation results in AMPK inhibition through activation of Lyn-Syk-Akt pathway, and as such FcεRI receptor can efficiently propagate Lyn-mediated allergic signaling and response. These results provide important insights into the use of AMPK activators for the treatment of allergic diseases. KEY MESSAGES: AMPK is inhibited by FcεRI via Lyn-Syk-Akt signaling in RBL-2H3 cells. AMPK inhibition supports FcεRI-mediated Lyn signaling and allergic response. Metformin has inhibitory effect on passive cutaneous anaphylaxis.

[Characteristics of dominant tree species stem sap flow and their relationships with environmental factors in a mixed conifer-broadleaf forest in Dinghushan, Guangdong Province of South China].

By the method of Granier' s thermal dissipation probe, the stem sap flow density of four dominant tree species (Pinus massoniana, Castanopsis chinensis, Schima superba, and Machilus kwangtungensis) in a mixed conifer-broadleaf forest in Dinghushan Reserve of South China was continuously measured in the dry season (November) and wet season (July) in 2010, and the environmental factors including air temperature, relative humidity, and photosynthetically active radiation (PAR) were measured synchronically, aimed to study the characteristics of the stem sap flow of the tree species in response to environmental factors. During the dry and wet seasons, the diurnal changes of the stem sap flow velocity of the tree species all presented a typical single-peak curve, with high values in the daytime and low values in the nighttime. The average and maximum sap flow velocities and the daily sap flow flux of broad-leaved trees (C. chinensis, S. superba, and M. kwangtungensis) were significantly higher than those of coniferous tree (P. massoniana), and the maximum sap flow velocity of P. massoniana, C. valueschinensis, S. superba, and M. kwangtungensis was 29.48, 38.54, 51.67 and 58.32 g H2O x m(-2) x s(-1), respectively. A time lag was observed between the sap flow velocity and the diurnal variations of PAR, vapor pressure deficiency, and air temperature, and there existed significant positive correlations between the sap flow velocity and the three environmental factors. The PAR in wet season and the air temperature in dry season were the leading factors affecting the stem sap flow velocity of the dominant tree species.