[Janus kinase 3 facilitates the migration of breast cancer cells by store-operated calcium channel].

The present study was aimed to investigate the effect of Janus kinase 3 (JAK3) on the migration of breast cancer cells and the underlying mechanism. The expression of JAK3 in breast cancer MCF-7 cells was silenced by siRNA (siJAK3). The migration ability of MCF-7 cells was detected by scratch test. The activity of store-operated calcium channel (SOCC) was detected by fluorescence calcium imaging. The expression levels of Orai1 and STIM1, key molecules in the process of store-operated calcium entry (SOCE) were detected by Western blot and RT-PCR. The results showed that 2-APB, an inhibitor of SOCC, could inhibit the migration ability of MCF-7 cells. siJAK3 transfection significantly inhibited the migration ability of MCF-7 cells, decreased the activity of SOCC, and down-regulated mRNA and protein expression levels of Orai1 and Stim1. Over-expression of Orai1 or STIM1 in JAK3-silenced cells restored their migration ability. These results suggest that JAK3 facilitates the migration of breast cancer cells by SOCC.

Leucine-rich repeat kinase 2 regulates mouse dendritic cell migration by ORAI2.

The leucine-rich repeat kinase 2 (LRRK2) is expressed in various immune cells and involved in regulating inflammatory processes. LRRK2 facilitates calcium extrusion exchanger and sodium-calcium exchanger activity and hence influences intracellular Ca2+ concentration in dendritic cells (DCs). DC maturation and migration are governed by the intracellular Ca2+ concentration, but the related mechanisms whereby LRRK2 regulates DC function and involved Ca2+ channels are still under investigation. In the previous study, we found that LRRK2-/- DCs exhibited higher store-operated Ca2+ entry (SOCE) activity than LRRK2+/+ DCs. Herein, we ascertained the exact SOCE components by using genetic, pharmacological, and fluorescent approaches. Ca2+ imaging showed that LRRK2 kinase activity negatively modulated SOCE activity. Moreover, LRRK2 deficiency resulted in an enhanced migration capacity of DCs but had little effect on the maturation process. SOCE is widely known to regulate DC functions; we wanted to dissect the reason why LRRK2 specifically influenced DC migration and therefore silenced ORAI1, ORAI2, and ORAI3, respectively. Transwell assays showed that both ORAI1 and ORAI2 silencing markedly decreased the migration of DCs, but only ORAI1 deficiency influenced the expression of maturation markers CD11c, CD86, and major histocompatibility complex class II. Of note, LRRK2 deficiency increased ORAI2 expression but not that of ORAI1 and ORAI3. Thus, we suggest that LRRK2 modulates DC migration by interfering with ORAI2.-Yan, J., Zhao, W., Gao, C., Liu, X., Zhao, X., Wei, T., Gao, Z. Leucine-rich repeat kinase 2 regulates mouse dendritic cell migration by ORAI2.

[Size distribution of carbonaceous particulate matter in atmosphere of Shanghai, China].

Using STAPLEX pumping system with a six-stage cascade impactor (size range: <0.49 microm, 0.49-0.95 microm, 0.95-1.5 microm, 1.5-3.0 microm, 3.0-7.2 microm, > 7.2 microm), the atmospheric particulate samples at suburb (Jiading District) and urban (Xuhui District) sites in Shanghai, China were collected from May 2010 to May 2011. The organic carbon (OC) and the element carbon (EC) of those samples were analyzed by a DRI Model 2001 thermal/optical carbon analyzer with the reflectance (TOR) method. The size distributions of OC and EC in atmospheric particles both showed bimodal distributions at Jiading and Xuhui, with the peaks at size range of < 0.49 microm. Meanwhile, the average annual concentrations of OC and EC in PM3.0 were 16.35 microg x m(-3) and 2.22 microg x m(-3) at Jiading, 11.85 microg x m(-3) and 1.91 microg x m(-3) at Xuhui, respectively. The higher concentrations of particulate matters together with their carbonaceous species at the suburb site indicated that the particulate and carbonaceous aerosol pollution was more serious at suburb than at urban in Shanghai. Compared with Xuhui, the OC shared a higher homology with EC at < 1.5 microm sizes at Jiading, which suggested that OC was mostly derived from combustion sources at urban site in Shanghai. Furthermore, the OC/EC mass ratios at various particulate sizes and those ratios of different sources were discussed. The result suggested that more vehicle emission and more road dust were present at Xuhui District. Moreover, the second organic carbon (SOC) were estimated using EC as a tracer of primary organic carbon, the SOC mass concentration in PM3.0 was 6.76 microg x m(-3) and had a proportion of 69% of OC in Shanghai, which also showed a bimodal distribution with peaks at size of 0. 49-0.95 microm and 3.0-7.2 microm, respectively.