Recent studies suggest that carbon monoxide (CO) is another gas molecule that has similar biological actions as nitric oxide (NO). The purpose of this study is to investigate the relationship between NO and CO in the survival of naïve rat pheochromocytoma PC12 cells. Western blot analysis revealed that all three isoforms of nitric oxide synthase (NOS) exhibited low expression and two isoforms of heme oxygenase (HO), especially HO-1, exhibited higher expression in PC12 cells under basal condition. Exposure of PC12 cells for 24 h to the NO scavenger, carboxy-2-phenyl-4,4,5,5,- tetramethylimidazoline-1-oxy-1-3-oxide (carboxy-PTIO, 2 £gmol) or HO inhibitor, zinc protoporphyrinIX (ZnPP, 25 nmol) resulted in a progressive reduction in mitochondria dehydrogenase activity reflected cell viability as determined by the WST-1 (4-[3-(4-lodophenyl)- 2-(4-nitrophenyl)-2H-5-tetrazolio]-1,3-benzene disulfonate) assay. On the other hand, incubation with NO donors, amino-3-morpholinyl- 1,2,3-oxadiazolium chloride (SIN-1, 1 £gmol) or S-Nitroso-N-acetyl- penicillamine (SNAP, 1 £gmol), or the CO precursor, hematin (500 nmol), resulted in an elevation in cell viability. The progressive reduction in cell viability induced by carboxy-PTIO (2 £gmol) or ZnPP (25 nmol) was significantly blunted by co-treatment with SIN-1 (1 £gmol). However, incubation with the NO precursor, L-arginine (L-Arg, 2 £gmol), or the selective inhibitors for nNOS, iNOS or eNOS, N£s-propyl-L-arginine (NPLA, 100 pmol), S-methylisothiourea (SMT, 10 nmol) or N5-1-Iminoethyl-L-ornithine dihydrochloride (L-NIO, 4 nmol) did not significantly alter cell viability. Co-treatment with carboxy-PTIO (2 £gmol) and L-Arg (2 £gmol) was also ineffective. These results suggest that NO or CO contributes to the survival of naïve PC12 cells.

Carbon monoxide (CO) has been identified as an endogenous biological messenger in the brain. Heme oxygenase (HO) catalyzes the metabolism of heme to CO and biliverdin. CO has been shown to act as a neurotransmitter and neuronal messenger in the brain. We reported recently that CO was involved in central cardiovascular regulation, modulated the baroreflex, may affect glutamatergic neurotransmission, and metabotropic glutamate receptors (mGluRs) may be coupled to the activation of HO in the nucleus tractus solitarii (NTS) of rats. We also reported previously that adenosine can increase the release of glutamate in the NTS. The present study was designed to investigate the possible interaction of CO, adenosine, and mGluRs groups in the NTS. Male Sprague-Dawley rats were anesthetized with urethane, and blood pressure were monitored intra-arterially. Unilateral microinjection of ascending doses of hemin (0.01 to 3.3 nmol), a heme molecule cleaved by HO to yield CO, produced decreases in blood pressure and heart rate dose-dependently. In addition, similar cardiovascular effects were observed in adenosine (2.3 nmol) and several agonists for mGluRs groups such as DHPG (group ¢¹) (0.03 nmol), APDC (group ¢º) (0.3 nmol)and L-AP4 (group ¢») (0.3 nmol). These cardiovascular effects of hemin were attenuatd by prior administration of the adenosine receptor antagonist DPSPX (0.92 nmol). Similarly, pre-treatment of HO inhibitor ZnPP¢Á or ZnDPBG (1 nmol) also attenuated the depressor and bradycadic effects of adenosine. Among the mGluRs agonists, prior administration of ZnPP¢Á (1 nmol), an inhibitor of HO activity, significantly attenuated the cardiovascular effects of APDC and L-AP4, and failed to prevent the cardiovascular responses of DHPG. These results indicated an interaction between CO and adenosine, and group ¢º and ¢» mGluRs may be coupled to the activation of HO in central cardiovascular regulation.

Gold used to be regarded as catalytically inert until about 20 years ago when it was shown that supported gold clusters < 5 nm in diameter exhibited some unique catalytic properties. Based on this revelation, several studies have demonstrated the feasibility of reactions previously thought of as impossible on gold. The ability of gold to oxidize CO below ambient temperatures at rates higher than conventional CO oxidation catalysts (Pd and Pt) has been shown to hold potentials for technological applications. Extensive past and on-going research are geared towards elucidating the mechanistic details of this reaction. The nature of the active sites, the effect of the supports and the effect of moisture are still debated in literature. I therefore present some experimental results supported with density functional theory calculations to shed additional light on some of the issues concerning gold catalysis in general, and low temperature CO oxidation in particular. Previous studies of the effect of moisture on oxide-supported gold reported that although water promotes CO oxidation on this surface by as much as two orders of magnitude, it is only a spectator molecule on the surface. I present here evidence for strong water-oxygen interactions when water is co-adsorbed with atomic oxygen on Au(111). Impinging a CO beam on the surface co-adsorbed with oxygen and water produces water-enhanced CO oxidation. Based on these results, I propose that CO reacts with hydroxyls formed from water-oxygen interactions to form CO₂, similar to a previous observation on Pt(111). Exposing a Au(111) surface pre-covered with ¹⁶O to isotopically labeled carbon dioxide (C¹⁸O₂) showed that ¹⁶O¹⁸O (m/e = 34) was produced from carbonate formation and decomposition. Estimates of reaction probability and activation energy gave ~ 10⁻⁴ - 10⁻⁵ and -0.15 eV respectively. The effect of annealing on the reactivity of oxygen pre-covered Au(111) was investigated using water, carbon monoxide and carbon dioxide as probe molecules. Precovering Au(111) with atomic oxygen followed by annealing resulted in surfaces that were less reactive towards water, CO and CO₂. Annealing is believed to stabilize the reactive metastable oxygen thereby increasing the barrier to reaction similar to what is reported on other surfaces. / text

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Pre-eclampsia (PE) is a pregnancy disorder that affects roughly 5-7% of all pregnancies and is a leading cause of both maternal and fetal/neonatal morbidity and mortality. With no present cure for the disease, researchers are interested in the lower incidence of PE observed among the cigarette smoking pregnant population. However, women who use smokeless tobacco do not experience the same decreased incidence of PE, leading to hypothesis of protection against PE from the largest combustible product of cigarette smoke, carbon monoxide (CO). Studies evaluated levels of CO in PE women and found that they were statistically lower than those of healthy pregnancy. Researchers have found CO to possess many cytoprotective and regulatory properties and specifically within the placenta, it has been found to increase perfusion pressure, decrease oxidative stress, decreases ischemia/reperfusion induced apoptosis and maintain endothelial functioning. The idea for use of CO as a possible therapeutic for PE has thus become a real possibility. This study determined CO levels in pregnant women ± smoking as well as in PE women±smoking, as to discover a possible therapeutic range for future treatments. The best correlated automated CO measurement device with blood CO levels was determined, for use in future clinical studies. This thesis also sought a possible CO delivery concentration, in order to achieve the CO levels observed in the human correlation study. A threshold level of maternal CO exposure in a murine animal model was found, for which fetal and maternal negative toxicities were not observed. The results of this thesis lend a few more pieces to the complicated puzzle involving CO and PE and offer another step toward the possibility of a therapeutic treatment/prevention using this gaseous molecule. / Thesis (Master, Anatomy & Cell Biology) -- Queen's University, 2009-09-19 08:55:06.548

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