Search results for "GMP"

Nitric oxide increases the decay of matrix metalloproteinase 9 mRNA by inhibiting the expression of mRNA-stabilizing factor HuR.

2003

Dysregulation of extracellular matrix turnover is an important feature of many inflammatory processes. Rat renal mesangial cells express high levels of matrix metalloproteinase 9 (MMP-9) in response to inflammatory cytokines such as interleukin-1 beta. We demonstrate that NO does strongly destabilize MMP-9 mRNA, since different luciferase reporter gene constructs containing the MMP-9 3' untranslated region (UTR) displayed significant reduced luciferase activity in response to the presence of NO. Moreover, by use of an in vitro degradation assay we found that the cytoplasmic fractions of NO-treated cells contained a higher capacity to degrade MMP-9 transcripts than those obtained from contro…

Characterization of Membrane-Bound Cyclic Nucleotide Phosphodiesterases from Bovine Aortic Smooth Muscle

1992

This study reports the isolation and characterization of cyclic nucleotide phosphodiesterases (PDEs) associated with membrane fraction in comparison to cytosolic forms from bovine aorta. DEAE-Sephacel chromatography of a solubilized membrane fraction from a homogenate, prepared under isotonic conditions in the presence of protease inhibitors, yielded one major peak of PDE activity that specifically hydrolyzed cAMP and was not stimulated by calmodulin: It appeared to contain two subtypes of PDE. The first subtype belonged to the cyclic GMP (cGMP)-inhibited PDE family, (PDE III): It had an apparent Km value of 0.4 microM and was potently inhibited by cGMP, LY186126, and cilostamide. The secon…

Biochemistry and pharmacology of novel anthranilic acid derivatives activating heme-oxidized soluble guanylyl cyclase.

2005

The heme-enzyme soluble guanylyl cyclase (sGC) is an ubiquitous NO receptor, which mediates NO downstream signaling by the generation of cGMP. We studied the mechanism of action of the anthranilic acid derivatives 5-chloro-2-(5-chloro-thiophene-2-sulfonylamino-N-(4-(morpholine-4-sulfonyl)-phenyl)-benzamide sodium salt (HMR1766) (proposed international nonproprietary name, ataciguat sodium) and 2-(4-chloro-phenylsulfonylamino)-4,5-dimethoxy-N-(4-(thiomorpholine-4-sulfonyl)-phenyl)-benzamide (S3448) as a new class of sGC agonists. Both compounds activated different sGC preparations (purified from bovine lung, or crude from human corpus cavernosum) in a concentration-dependent and quickly reve…

The evolution of nitric oxide signalling diverges between the animal and the green lineages

2019

AbstractNitric oxide (NO) is a ubiquitous signalling molecule with widespread distribution in prokaryotes and eukaryotes where it is involved in countless physiological processes. While the mechanisms governing nitric oxide (NO) synthesis and signalling are well established in animals, the situation is less clear in the green lineage. Recent investigations have shown that NO synthase, the major enzymatic source for NO in animals, is absent in land plants but present in a limited number of algae. The first detailed analysis highlighted that these new NO synthases are functional but display specific structural features and probably original catalytic activities. Completing this picture, analy…

Modulación de la vía Glu-NO-GMPc y del aprendizaje por GMPc extracelular en cerebelo. Mecanismos moleculares implicados. Alteraciones en modelos anim…

2014

En modelos animales de hiperamonemia y encefalopatía hepática (EH) está disminuida la capacidad de aprendizaje de un test de discriminación condicionada en el laberinto en Y. La infusión crónica intracerebral de GMPc mediante bombas osmóticas restaura la capacidad de aprendizaje en el laberinto en Y en ratas con hiperamonemia crónica. El mecanismo por el que el GMPc extracelular modula la capacidad de aprendizaje no se conoce. La vía glutamato (Glu)-óxido nítrico (NO)-GMPc modula el aprendizaje en el laberinto en Y. La función de esta vía está alterada en modelos animales de hiperamonemia y EH, conduciendo a una disminución de la capacidad de aprendizaje en el laberinto en Y. Puesto que la …

Expression of Nitric Oxide Synthase I Determines the Strength of Adrenergic Cyclic GMP Response in the Rat Pineal Gland

1997

In the rat pineal gland the adrenergic cGMP response is not static but changes during postnatal development and depends on environmental lighting conditions. Since the adrenergic cGMP transduction is mediated by stimulation of the enzyme nitric oxide synthase I (NOS I), we investigated whether changes in the strength of adrenergic cGMP response coincide with the expression of NOS I. Using immunoblot analysis, we found that the increase in adrenergic cGMP transduction in the second postnatal week coincides with enhanced NOS I expression. Similarly, we observed that changes in the intensity of adrenergic cGMP transduction under different environmental lighting conditions correspond to NOS I e…

Interaction of glutamic-acid-rich proteins with the cGMP signalling pathway in rod photoreceptors.

1999

The assembly of signalling molecules into macromolecular complexes (transducisomes) provides specificity, sensitivity and speed in intracellular signalling pathways. Rod photoreceptors in the eye contain an unusual set of glutamic-acid-rich proteins (GARPs) of unknown function. GARPs exist as two soluble forms, GARP1 and GARP2, and as a large cytoplasmic domain (GARP' part) of the beta-subunit of the cyclic GMP-gated channel. Here we identify GARPs as multivalent proteins that interact with the key players of cGMP signalling, phosphodiesterase and guanylate cyclase, and with a retina-specific ATP-binding cassette transporter (ABCR), through four, short, repetitive sequences. In electron mic…

Biotekniikan avulla tuotettujen lääkkeiden teollista valmistusta koskeva lainsäädäntö Suomessa

2004

Hyperglycemia and oxidative stress in cultured endothelial cells – a comparison of primary endothelial cells with an immortalized endothelial cell li…

2012

Diabetes mellitus is a major risk factor for the development of cardiovascular disease and oxidative stress plays an important role in this process. Therefore, we investigated the effects of hyperglycemia on the formation of reactive oxygen species (ROS) and nitric oxide/cGMP signaling in two different endothelial cell cultures. Human umbilical vein endothelial cells (HUVEC) and EA.hy 926 cells showed increased oxidative stress and impaired NO-cGMP signaling in response to hyperglycemia. The major difference between the two different cell types was the dramatic decrease in viability in HUVEC whereas EA.hy cells showed rather increased growth under hyperglycemic conditions. Starvation led to…

Effects of inhibitors of cGMP-dependent protein kinase in atrial heart and aortic smooth muscle from rats

1995

Several activators of cGMP-dependent protein kinase (protein kinase G) such as 8-Br-cGMP reduced force of contraction in rat left atria. Inhibitors of protein kinase G antagonized the negative inotropic effect of 8-Br-cGMP but not of acetylcholine in atria. However, the acetylcholine-induced relaxation in aortic rings was significantly inhibited by protein kinase G inhibition. It is concluded that the reduction by 8-Br-cGMP of force of contraction in atria is related to activation of protein kinase G. In response to acetylcholine, activation of protein kinase G is probably a major step in smooth muscle relaxation but is not involved in the reduction of force of contraction in atria.