ABSTRACT
We present the synthesis, structural characterization, and magnetic properties of two high-nuclearity cobalt clusters formulated as [Co13(µ3-OH)3(µ3-Cl)(dpbt)5(ptd)Cl10][Co(H2O)2Cl2]·(CH3)2CHOH (1) and [Co24(µ3-OH)6(µ3-Cl)2(dpbt)10(ptd)2Cl16]·2CH3CH2OH (2), respectively (H2dpbt = 5,5'-bis(pyridin-2-yl)-3,3'-bis(1,2,4-triazole) and H2ptd = 3-(pyridin-2-yl)-1,2,4-triazine-5,6-diol). Compound 1 is composed of an inner [Co4(µ3-OH)3(µ3-Cl)] cubane and an outer [Co9(dpbt)5(ptd)Cl10] defective adamantane. Compound 2 reveals a giant {Co24} cluster possessing a dual-[Co12] skeleton from 1. The hierarchical assembly from 1 to 2 has been established and tracked through high-resolution electrospray ionization (HRESI-MS) analyses from the solvothermal reaction mother solution. Magnetic studies of 1 and 2 revealed the highly correlated spins, a glasslike magnetic phase transition at ca. 8 K, and slow relaxation behavior of SMM nature in the lower-temperature region (below 4 K).
ABSTRACT
Oxsterol binding protein-related protein 4 (ORP4) is essential for cell proliferation, but the underlying mechanism is unclear. ORP4 is expressed as three variants, ORP4L, ORP4M and ORP4S. Here, we reported that silencing of ORP4L with specific small interfering RNA (siRNA) inhibited the proliferation of human cervical cancer cell lines C33A, HeLa and CaSki, the reverse effect being observed in ORP4L overexpressing cells. For molecular insight, we found that ORP4L maintained intracellular Ca2+ homeostasis. Through this mechanism, ORP4L activated nuclear factor of activated T cells (NFAT) activity and thus promoted expression of a gene cluster which supported cell proliferation. Of note, ORP4L sustained inositol-1,4,5-trisphosphate receptor 1 (IP3R1) expression at both mRNA and protein levels via Ca2+-dependent NFAT3 activation, which offered a mechanic explanation for the role of ORP4L intracellular Ca2+ homeostasis. Furthermore, ORP4L knockdown markedly inhibited tumor growth in a C33A cell xenograft mouse model. To conclude, our results reveal that ORP4L promotes cell proliferation through maintaining intracellular Ca2+ homeostasis.
Subject(s)
Biomarkers, Tumor/metabolism , Calcium/metabolism , Cell Proliferation , Homeostasis/physiology , Inositol 1,4,5-Trisphosphate Receptors/metabolism , Receptors, Steroid/metabolism , Uterine Cervical Neoplasms/pathology , Animals , Apoptosis , Biomarkers, Tumor/genetics , Cytoplasm/metabolism , Female , Humans , Inositol 1,4,5-Trisphosphate Receptors/genetics , Male , Mice , Mice, Inbred BALB C , Mice, Nude , NFATC Transcription Factors/genetics , NFATC Transcription Factors/metabolism , Oxysterols/metabolism , Protein Isoforms , Receptors, Steroid/genetics , Tumor Cells, Cultured , Uterine Cervical Neoplasms/genetics , Uterine Cervical Neoplasms/metabolism , Xenograft Model Antitumor AssaysABSTRACT
PURPOSE: The objectives of this study were to explore the factors influencing urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels in diesel engine exhaust emission inspectors (inspectors), the association between polycyclic aromatic hydrocarbons (PAHs) exposure and fine particulate matter (PM(2.5)) levels in diesel exhaust particles (DEPs), and the PAHs exposure levels in diesel vehicle emission inspection stations (inspection stations). METHODS: Twenty-eight inspectors and a control group of thirty-eight individuals matched by age and gender were recruited for this study. Fifteen ambient air samples and eighty-four personal air samples were monitored during 3-day work periods using a repeated-measures study design in each inspection station. Airborne samples were analyzed with a fluorescence detector and by high-performance liquid chromatography. Urinary 8-OHdG was measured in 168 pre- and post-work urine samples from inspectors, and in 38 urine samples from controls. RESULTS: The concentrations of PAHs in DEP(2.5) (PM(2.5) in DEPs) were significantly and positively related to urinary log(10) 8-OHdG levels after adjusting for smoking status and BMI. Statistically, there was a significant correlation between air log(10) PAHs and air log(10) PM(2.5) concentrations in inspectors. Fifteen PAHs compounds within DEP(2.5) revealed the concentrations ranged from 5.18 to 22.93 ng/m(3) in ambient air monitoring and 1.03 to 12.60 ng/m(3) in personal air monitoring. CONCLUSIONS: This study is the first to indicate an association between occupational PAHs exposure from DEP(2.5) at an inspection station and an increased excretion of urinary 8-OHdG in inspectors. In addition, this study also found smoking is not a confounder in inspectors exposed to PAHs in DEP(2.5).
