No abstract available

[en] Exposure to traffic-related air pollution (TRAP) has been linked to childhood anxiety symptoms. Neuroimaging in patients with anxiety disorders indicate altered neurochemistry.

[en] We have successfully synthesized the polystyrene carrying a conformationally rigid myo-inositol substituent as a possible metal-chelating ligand. We are further investigating the metal binding properties of this polymer and its applicability to the practical use such as molecular imprinting. Compounds having three syn-axial hydroxyl groups on a six membered ring draw an interest due to their ability to form complexes with many cations. The steric requirements of the cyclohexane polyols to form complexes with cations are, however, rather strict and only a few such compounds with three syn-axial hydroxyls, including cis-inositol, were known. Moreover, none of these compounds is readily available, especially in large scales. Recently, synthesis of the readily available myo-inositol 4,6-carbonate with three hydroxyl groups at the axial position on a cyclohexane was reported. To our knowledge, this was the first example of the conformationally rigid cyclohexane polyols using the readily available myo-inositol

[en] The inositol-signaling pathway is a therapeutic target for lithium in the treatment of bipolar disorder. Inositol monophosphatases (IMPases) play a key role in inositol signaling. Lithium's ability to inhibit IMPase 1 is well known, but its effect on IMPase 2 or on the transcriptional regulation of these genes has not been studied. Here, we report the identification and characterization of the minimal promoter of IMPA2 (encoding IMPase 2) in HeLa (epithelial) and SK-N-AS (neuronal) cells. IMPA2 promoter activity appears to be contributed by different elements in the 5' flanking region, suggesting that the gene is differentially regulated in neuronal and non-neuronal cells. Furthermore, IMPA2 promoter activity in both cell lines is downregulated, in a dose-dependent manner, by lithium after treatment for only 24 h. This effect is also observed in vivo. Our results suggest a possible role for IMPA2 in bipolar disorder

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No abstract available

[en] The phospholipid hydrolase phospholipase Cγ1 (PLCγ1) plays a major role in regulation of cell proliferation, development, and cell motility. Overexpression of PLCγ1 is associated with tumor development, and it is overexpressed in some tumors. Matrix metalloproteinase-3 (MMP-3) is a protein involved in tumor invasion and metastasis. Here, we demonstrate that overexpression of PLCγ1 stimulates MMP-3 expression at the transcriptional level via the PKC-mediated Raf/MEK1/ERK signaling cascade. We propose that modulation of PLCγ1 activity might be of value in controlling the activity of MMPs, which are important regulators of invasion and metastasis in malignant tumors

[en] As the most conserved branch of the unfolded protein response (UPR), the inositol-requiring enzyme 1a (IRE1a)/X-box binding protein 1 (XBP1) pathway plays crucial roles in cell survival and cell death by upregulating UPR-associated genes involved in protein entry into the endoplasmic reticulum (ER) and ER-associated degradation (ERAD). Selenoprotein S (SelS) is localized to the ER membrane and involved in ERAD. Although SelS plays an important role in restoring ER stress, the SelS-dependent protective mechanisms against cell death remain unclear. Here, using an inducible SelS knockdown (KD) 3T3-L1 cell model, we showed that SelS KD resulted adipocyte death, which was associated with imbalance of the Bcl-2 family members. Furthermore, SelS KD decreased spliced XBP1 (sXBP1), increased IRE1α and p-JNK, suggesting a role of SelS in the modulation of the IRE1α-sXBP1 pathway. Moreover, adipocyte death induced by SelS suppression can be inhibited by overexpression of sXBP1. Thus, it is proposed that SelS promotes cell survival through the IRE1α-XBP1 signaling pathway.

[en] We reported increased levels of Phosphatidyl Inositol synthase (PI synthase), (enzyme that catalyses phosphatidyl inositol (PI) synthesis-implicated in intracellular signaling and regulation of cell growth) in smokeless tobacco (ST) exposed oral cell cultures by differential display. This study determined the clinical significance of PI synthase overexpression in oral squamous cell carcinoma (OSCC) and premalignant lesions (leukoplakia), and identified the downstream signaling proteins in PI synthase pathway that are perturbed by smokeless tobacco (ST) exposure. Tissue microarray (TMA) Immunohistochemistry, Western blotting, Confocal laser scan microscopy, RT-PCR were performed to define the expression of PI synthase in clinical samples and in oral cell culture systems. Significant increase in PI synthase immunoreactivity was observed in premalignant lesions and OSCCs as compared to oral normal tissues (p = 0.000). Further, PI synthase expression was significantly associated with de-differentiation of OSCCs, (p = 0.005) and tobacco consumption (p = 0.03, OR = 9.0). Exposure of oral cell systems to smokeless tobacco (ST) in vitro confirmed increase in PI synthase, Phosphatidylinositol 3-kinase (PI3K) and cyclin D1 levels. Collectively, increased PI synthase expression was found to be an early event in oral cancer and a target for smokeless tobacco

[en] Both natural D- and L-enantiomers of myo-Ins(1,4,5)P₃ were synthesized with specific activities 14-16 Ci/mmol. A suitable inositol derivative was resolved as the diastereomeric camphanate esters, and the chiral inositol derivatives were oxidized to the protected inosose. Reduction of each chiral ketone with sodium borotritide and manipulation of protecting groups gave the enantiomeric [1-³H]-2,3,6-tri-O-benzyl-myo-inositols in 55% radiochemical yield. Phosphorylation with tetrabenzylpyrophosphate and complete hydrogenolytic debenzylation provided the separate D-myo and L-myo-[1-³H]-Ins(1,4,5)P₃ enantiomers in 30% radiochemical yield. (author)