Queuine Micronutrient Deficiency Promotes Warburg Metabolism and Reversal of the Mitochondrial ATP Synthase in Hela Cells.

Queuine is a eukaryotic micronutrient, derived exclusively from eubacteria. It is incorporated into both cytosolic and mitochondrial transfer RNA to generate a queuosine nucleotide at position 34 of the anticodon loop. The transfer RNA of primary tumors has been shown to be hypomodified with respect to queuosine, with decreased levels correlating with disease progression and poor patient survival.

Defects in NADPH Oxidase Genes and in Very Early Onset Inflammatory Bowel Disease.

Background & Aims: Defects in intestinal innate defense systems predispose patients to inflammatory bowel disease (IBD). Reactive oxygen species (ROS) generated by nicotinamide-adenine dinucleotide phosphate (NADPH) oxidases in the mucosal barrier maintain gut homeostasis and defend against pathogenic attack. We hypothesized that molecular genetic defects in intestinal NADPH oxidases might be present in children with IBD.

RhoA determines disease progression by controlling neutrophil motility and restricting hyperresponsiveness.

Neutrophil responses are central to host protection and inflammation. Neutrophil activation follows a 2-step process in which priming amplifies responses to activating stimuli. Priming is essential for life span extension, chemotaxis, and respiratory burst activity.

Mucosal reactive oxygen species are required for antiviral response: role of Duox in influenza a virus infection.

Aims: Influenza A virus (IAV), a major airborne pathogen, is closely associated with significant morbidity and mortality. The primary target for influenza virus replication is the respiratory epithelium, which reacts to infection by mounting a multifaceted antiviral response. A part of this mucosal host defense is the generation of reactive oxygen species (ROS) by NADPH oxidases.

Balancing reactive oxygen species in the epigenome: NADPH oxidases as target and perpetrator.

Significance: NADPH oxidases are important sources for regulated generation of reactive oxygen species (ROS). The main ROS produced are superoxide and hydrogen peroxide, both of which are redox signaling molecules in the context of various cellular functions. Redox imbalance due to excessive or insufficient ROS is a hallmark of pathophysiological aspects, including cancer development and progression.

Constitutive NADPH oxidase 4 activity resides in the composition of the B-loop and the penultimate C terminus.

Redox regulation of signaling molecules contributes critically to propagation of intracellular signals. The main source providing reactive oxygen species (ROS) for these physiological processes are activated NADPH oxidases (Nox/Duox family). In a pathophysiological context, some NADPH oxidase complexes produce large amounts of ROS either as part of the antimicrobial immune defense or as pathologic oxidative stress in many chronic diseases.

Queuosine formation in eukaryotic tRNA occurs via a mitochondria-localized heteromeric transglycosylase.

tRNA guanine transglycosylase (TGT) enzymes are responsible for the formation of queuosine in the anticodon loop (position 34) of tRNA(Asp), tRNA(Asn), tRNA(His), and tRNA(Tyr); an almost universal event in eubacterial and eukaryotic species. Despite extensive characterization of the eubacterial TGT the eukaryotic activity has remained undefined. Our search of mouse EST and cDNA data bases identified a homologue of the Escherichia coli TGT and three spliced variants of the queuine tRNA guanine transglycosylase domain containing 1 (QTRTD1) gene.