[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] Published in summary form only

[en] Autoradiographic techniques were used to investigate the characteristics of tritiated inositol(1,4,5)trisphosphate ([³H]IP₃) and inositol(1,2,3,4,5)tetrakisphosphate ([³H]IP₄) binding to human brain. In brain sections ([³H]IP₃) exhibited a two-site binding with K_D values of 87 nM and 9.3 μM respectively for the higher and lower affinity sites. [³H]IP₄, also bound to two sites with K_D values of 43 nM and 1.4 μM. respectively. With the conditions fixed in this study, [³H]IP₃ and [³H]IP₄ autoradiography in the cortex, caudate, hippocampus and cerebellum were performed. The most prominent [³H]IP₃ binding among these regions was found in the cerebellum, particularly in the molecular layer. Within the hippocampus, the subiculum and the CA1 region showed much more prominent binding than the other subfields. [³H]IP₄ binding was fairly homogeneous in the regions studied, with the exception of a slightly higher binding in the molecular layer of the cerebellum. (author)

[en] Highlights: • IP₃ receptor type 1 (IP₃R1) are expressed in atrial cell perinucleus. • IP₃R1 mediates ATP-induced sustained nuclear Ca²⁺ increase in HL-1 atrial cells. • IP₃R1 contributes to higher sensitivity of nuclear release sites upon IP₃ increase. • Larger Ca²⁺ content in perinuclear store of atrial cells involves IP₃R1. • IP₃R1 signaling may play a role in ATP-induced atrial cell hypertrophy. Inositol 1,4,5-trisphosphate receptor type 1 (IP₃R1) is expressed in atrial muscle, but not in ventricle, and they are abundant in the perinucleus. We investigated the role of IP₃R1 in the regulations of local Ca²⁺ signal and cell size in HL-1 atrial myocytes under stimulation by IP₃-generating chemical messenger, ATP. Assessment of nuclear and cytosolic Ca²⁺ signal using confocal Ca²⁺ imaging revealed that IP₃ generation by ATP (1 mM) induced monophasic nuclear Ca²⁺ increase, followed by cytosolic Ca²⁺ oscillation. Genetic knock-down (KD) of IP₃R1 eliminated the monophasic nuclear Ca²⁺ signal and slowed the cytosolic Ca²⁺ oscillation upon ATP exposure. Prolonged application of ATP as well as other known hypertrophic agonists (endothelin-1 and phenylephrine) increased cell size in wild-type cells, but not in IP₃R1 KD cells. Our data indicate that IP₃R1 mediates sustained elevation in nuclear Ca²⁺ level and facilitates cytosolic Ca²⁺ oscillation upon external ATP increase, and further suggests possible role of nuclear IP₃R1 in atrial hypertrophy.

[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] D-ononitol epimerase (OEP) catalyzes the conversion of D-ononitol to D-pinitol, which is the last step in the biosynthetic pathway, where myo-inositol is converted to pinitol in higher plants. In this study, OEP cDNA was isolated from Glycine max (GmOEP) and was functionally characterized, which confirmed that GmOEP expression was induced by high salinity and drought stress treatments. To understand the biological function of GmOEP, transgenic Arabidopsis plants overexpressing this protein were constructed. The transgenic Arabidopsis plants displayed enhanced tolerance to high salinity and drought stress treatments.

[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] Highlights: • RBC proteins interact with plasmodium RNA. • Human PIP4K2A from RBC can associate with plasmodium UTR sequences present in translationally regulated transcripts. • PIP4K2A from RBC is imported into the Plasmodium parasites. Plasmodium falciparum is a causative agent for malaria and has a complex life cycle in human and mosquito hosts. Translation repression of specific set of mRNA has been reported in gametocyte stages of this parasite. A conserved element present in the 3′UTR of some of these transcripts was identified. Biochemical studies have identified components of the RNA storage and/or translation inhibitor complex but it is not yet clear how the complex is specifically recruited on the RNA targeted for translation regulation. We used the 3′UTR region of translationally regulated transcripts to identify Phosphatidyl-inositol 5-phosphate 4-kinase (PIP4K2A) as the protein that associates with these RNAs. We further show that recombinant PIP4K2A has the RNA binding activity and can associate specifically with Plasmodium 3′UTR RNAs. Immunostainings show that hPIP4K2A is imported into the Plasmodium parasite from RBC. These results identify a novel RNA binding role for PIP4K2A that may play a role in Plasmodium propagation.

No abstract available

[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