Galectin-3 Negatively Regulates Hippocampus-Dependent Memory Formation through Inhibition of Integrin Signaling and Galectin-3 Phosphorylation.

Galectin-3, a member of the galectin protein family, has been found to regulate cell proliferation, inhibit apoptosis and promote inflammatory responses. Galectin-3 is also expressed in the adult rat hippocampus, but its role in learning and memory function is not known. Here, we found that contextual fear-conditioning training, spatial training or injection of NMDA into the rat CA1 area each dramatically decreased the level of endogenous galectin-3 expression. Overexpression of galectin-3 impaired fear memory, whereas galectin-3 knockout (KO) enhanced fear retention, spatial memory and hippocampal long-term potentiation. Galectin-3 was further found to associate with integrin α3, an association that was decreased after fear-conditioning training. Transfection of the rat CA1 area with small interfering RNA against galectin-3 facilitated fear memory and increased phosphorylated focal adhesion kinase (FAK) levels, effects that were blocked by co-transfection of the FAK phosphorylation-defective mutant Flag-FAKY397F. Notably, levels of serine-phosphorylated galectin-3 were decreased by fear conditioning training. In addition, blockade of galectin-3 phosphorylation at Ser-6 facilitated fear memory, whereas constitutive activation of galectin-3 at Ser-6 impaired fear memory. Interestingly galectin-1 plays a role in fear-memory formation similar to that of galectin-3. Collectively, our data provide the first demonstration that galectin-3 is a novel negative regulator of memory formation that exerts its effects through both extracellular and intracellular mechanisms.

Hes-1 SUMOylation by protein inhibitor of activated STAT1 enhances the suppressing effect of Hes-1 on GADD45α expression to increase cell survival.

BACKGROUND: Hairy and Enhancer of split 1 (Hes-1) is a transcriptional repressor that plays an important role in neuronal differentiation and development, but post-translational modifications of Hes-1 are much less known. In the present study, we aimed to investigate whether Hes-1 could be SUMO-modified and identify the candidate SUMO acceptors on Hes-1. We also wished to examine the role of the SUMO E3 ligase protein inhibitor of activated STAT1 (PIAS1) in SUMOylation of Hes-1 and the molecular mechanism of Hes-1 SUMOylation. Further, we aimed to identify the molecular target of Hes-1 and examine how Hes-1 SUMOylation affects its molecular target to affect cell survival. RESULTS: In this study, by using HEK293T cells, we have found that Hes-1 could be SUMO-modified and Hes-1 SUMOylation was greatly enhanced by the SUMO E3 ligase PIAS1 at Lys8, Lys27 and Lys39. Furthermore, Hes-1 SUMOylation stabilized the Hes-1 protein and increased the transcriptional suppressing activity of Hes-1 on growth arrest and DNA damage-inducible protein alpha (GADD45α) expression. Overexpression of GADD45α increased, whereas knockdown of GADD45αα expression decreased cell apoptosis. In addition, H2O2 treatment increased the association between PIAS1 and Hes-1 and enhanced the SUMOylation of Hes-1 for endogenous protection. Overexpression of Hes-1 decreased H2O2-induced cell death, but this effect was blocked by transfection of the Hes-1 triple sumo-mutant (Hes-1 3KR). Overexpression of PIAS1 further facilitated the anti-apoptotic effect of Hes-1. Moreover, Hes-1 SUMOylation was independent of Hes-1 phosphorylation and vice versa. CONCLUSIONS: The present results revealed, for the first time, that Hes-1 could be SUMO-modified by PIAS1 and GADD45α is a novel target of Hes-1. Further, Hes-1 SUMOylation mediates cell survival through enhanced suppression of GADD45α expression. These results revealed a novel role of Hes-1 in addition to its involvement in Notch signaling. They also implicate that SUMOylation could be an important posttranslational modification that regulates cell survival.

Precisely introducing defects into periodic structures by using a double-step laser scanning technique.

We demonstrate a promising method to precisely introduce desired defects into large-area periodic structures by using a double-step laser scanning technique. A multiexposure two-beam interference technique is first used to create 2D periodic structures. A low power femtosecond laser combined with a high numerical aperture objective lens is then used to map the periodic structures to determine the positions and orientations of air holes or material cylinders without intermediate development. Based on the mapping results, the desired defects are written precisely into these structures by increasing the power of the femtosecond laser to induce a multiphoton polymerization effect. The experimental results show that defects are patterned with accurate positions and orientations. This proposed technique should be useful for fabrication of photonic crystals with well-defined defects.

Fabrication of two- and three-dimensional periodic structures by multi-exposure of two-beam interference technique.

A simple and efficient optical interference method for fabricating high quality two- and three-dimensional (2D and 3D) periodic structures is demonstrated. Employing multi-exposure of two-beam interference technique, different types of periodic structures are created depending on the number of exposure and the rotation angle of the sample for each exposure. Square and hexagonal 2D structures are fabricated by a multi-exposure of two-beam interference pattern with a rotation angle of 90 masculine and 60 masculine between two different exposures, respectively. Three-exposure, in particular, results in different kinds of 3D structures, with close lattice constants in transverse and longitudinal directions, which is difficult to be obtained by the commonly used multi-beam interference technique. The experimental results obtained with SU-8 photoresist are well in agreement with the theoretical predictions. Multi-exposure of two-beam interference technique should be very useful for fabrication of photonic crystals.