NAD abhängige Signalwege Einleitung Die Pyridinnukleotide, Nikotinamidadenindinukleotid und Nikotinamidadenindinukleotidphosphat [NAD(P)], sind ubiquitär auftretende Coenzyme, die an zahlreichen Reaktionen der zellulären Energietransformation beteiligt sind. Seit langem ist ihre fundamentale Bedeutung als Cofaktoren vieler Dehydrogenasen, die Hydridtransferreaktionen zentral zum Energieumsatz katalysieren, bekannt. Mit der Entdeckung von Signalwegen, die durch Metabolite der oxidierten Formen [NAD(P)+] gesteuert werden, sind…

NAADP, CD38 und Ca2 Einleitung 1.1 Funktionen des nativen Immunsystems Um die Gefahr einer Infektion durch Bakterien, Viren, Würmer und anderer Pathogene zu minimieren, entwickelte sich in Säugetieren ein komplexes Verteidigungssystem, das Immunsystem, welches sich in das angeborene und das adaptive Immunsystem unterteilen lässt. Das angeborene Immunsystem besteht aus unterschiedlichen phagozytischen Zellen, zu denen unter…

Inhibition of NAD(P)H_quinone oxidoreductase NAD(P)H:quinone oxidoreductase 1 (NQO1) regulates the stability of the tumor suppressor WT p53. NQO1 binds and stabilizes WT p53, whereas NQO1 inhibitors including dicoumarol and various other coumarins and flavones induce ubiquitin-independent proteasomal p53 degradation and thus inhibit p53-induced apoptosis. Here, we show that curcumin, a natural phenolic compound found in…

In vivo multiphoton microscopy of NADH and FAD Metabolic imaging of the relative amounts of reduced NADH and FAD and the microenvironment of these metabolic electron carriers can be used to noninvasively monitor changes in metabolism, which is one of the hallmarks of carcinogenesis. This study combines cellular redox ratio, NADH and FAD lifetime, and…

In Vivo Analysis of the Mechanisms for Oxidation of Cytosolic NADH During respiratory glucose dissimilation, eukaryotes produce cytosolic NADH via glycolysis. This NADH has to be reoxidized outside the mitochondria, because the mitochondrial inner membrane is impermeable to NADH. In Saccharomyces cerevisiae, this may involve external NADH dehydrogenases (Nde1p or Nde2p) and/or a glycerol-3-phosphate shuttle…

Exogenous NAD Blocks Cardiac Hypertrophic Response Since the discovery of NAD-dependent deacetylases, sirtuins, it has been recognized that maintaining intracellular levels of NAD is crucial for the management of stress response of cells. Here we show that agonist-induced cardiac hypertrophy is associated with loss of intracellular levels of NAD, but not exerciseinduced physiologic hypertrophy. Exogenous…

Engineering of a functional human NADH-dependent cytochrome P450 system A functional human NADH-dependent cytochrome P450 system has been developed by altering the cofactor preference of human NADPH cytochrome P450 reductase (CPR), the redox partner for P450s. This has been achieved by a single amino acid change of the conserved aromatic amino acid Trp-676, which covers…

Energy dependence of restitution in the gastric mucosa Cheng, Aaron M., Sarah W. Morrison, David X. Yang, and Susan J. Hagen. Energy dependence of restitution in the gastric mucosa. Am J Physiol Cell Physiol 281: C430–C438, 2001.—Rapid epithelial repair (restitution) after injury is required to maintain barrier function of the gastrointestinal mucosa and skin and…

ENADANADH improves cognitive impairment of Alzheimer patients Although significant progress has been achieved in revealing the etiology of AD, the search for efficient therapy stays the main goal. Nicotinamide adenine dinucleotide (NADH) is biologically identified as a cofactor necessary for a number of cellular actions, such as energy production, cell regulation and DNA repair, enhancement…

Elevation of Cellular NAD Levels by Nicotinic Acid NAD plays critical roles in various biological processes through the function of SIRT1. Although classical studies in mammals showed that nicotinic acid (NA) is a better precursor than nicotinamide (Nam) in elevating tissue NAD levels, molecular details ofNADsynthesis fromNAremain largely unknown. We here identified NA phosphoribosyltransferase (NAPRT)…