Search results for "Endogeny"
showing 10 items of 147 documents
Nitroglycerin-induced cardioprotection is endothelial nitric oxide synthase- dependent
2015
Purpose We sought to evaluate the contribution of the endogenous NO pathway to the cardioprotective action of nitroglycerin (NTG). Methods and Results Anesthetized rabbits were subjected to 30-min myocardial ischemia (isc) and 3-h reperfusion (rep) and randomized into: Control group (no further intervention); PostC group (application of 8 cycles 30-sec isc/rep) and NTG treated group (2 μg/kg-1/min-1 IV bolus) for 65 min starting 10 min prior to rep. In additional groups, pharmacological inhibitors of NOS, nNOS, iNOS, PI3K, adenosine receptors and PKG were administrated with or without NTG. The infarcted (I) to risk (R) ratio was estimated. In a second experimental series tissue samples were…
ChemInform Abstract: Synthesis and in vitro Studies on a Potential Dopamine Prodrug.
2009
Dopamine delivery to the central nervous system (CNS) undergoes the permeability limitations of blood-brain barrier (BBB) which is a selective interface that excludes most water-soluble molecules from entering the brain. Neutral amino acids permeate the BBB by specific transport systems. Condensation of dopamine with neutral amino acids could afford potential prodrugs able to interact with the BBB endogenous transporters and easily enter the brain. The synthesis and characterization of the dopamine derivative 2-amino-N-[2-(3,4-dihydroxy-phenyl)-ethyl]-3-phenyl-propionamide (7) is described. The chemical and enzymatic stability of 7 was evaluated. The molecular weight (300 Da) and Log Papp (…
Peroxynitrite generated from constitutive nitric oxide synthase mediates the early biochemical injury in short-term cultured hepatocytes
2000
AbstractEarly loss of P450 in rat hepatocyte cultures appears directly related to nitric oxide (NO) overproduction. This study provides experimental evidence for the induction – shortly after isolation through the classical procedure – of strong oxidative stress that involves both oxygen-derived and NO-derived species. NO formation at this stage is due to the early activation of liver constitutive NO synthase (cNOS). Immunodetection of nitrated proteins provides direct evidence of endogenous peroxynitrite (PN) formation upon hepatocyte isolation. On the basis of the combined use of dihydrorhodamine 123 and NOS inhibitors, the analysis of the amount, time course and nature of the species inv…
Induction of DNA single-strand breaks by 131I and 99mTc in human mononuclear blood cells in vitro and extrapolation to the in vivo situation.
2000
The radionuclides (131)I and (99m)Tc are frequently used for therapy of benign and malignant thyroid disease ((131)I) and for diagnosis of thyroid and other diseases ((99m)Tc). However, the levels of DNA single-strand breaks (SSBs) induced in cells of patients after administration of (131)I and (99m)Tc are not known. In this study, we measured the number of SSBs per cell induced by (131)I and (99m)Tc in vitro, extrapolated the results to the clinical situation, and assessed their biological relevance by comparing levels of SSBs induced after therapeutic administration of (131)I and (99m)Tc to those induced by endogenous processes or by occupational exposure to genotoxic substances. A linear…
Role of Endogenous Oxidative DNA Damage in Carcinogenesis: What Can We Learn from Repair-Deficient Mice?
2002
Basal steady-state levels of oxidative DNA base modifications such as 7,8-dihydro-8-oxo-2'-deoxyguanosine (8-oxoG) are observed in all types of cells, most probably due to a continuous generation of reactive oxygen species (ROS) in the cellular oxygen metabolism, and it has long been suspected that they might play an important role in the initiation of carcinogenesis. Experimental evidence for this assumption can be obtained by studying the effects of a modulation of the steady-state levels, either by in- or decreasing the generation of oxidative DNA damage, on spontaneous mutation rates and cancer incidence. However, clear answers have not yet been obtained by these strategies. It is still…
Choline Fluxes to and from the Rat Cerebral Cortex Studied with the “Cup Technique” in Vivo
1986
Since MacIntosh and Oborin (11) and later Mitchell (12) introduced the “cup technique” as a mean to study acetylcholine release from the cerebral cortex in vivo, this technique has been widely used for investigating the release of various neurotransmitters in anaesthetized as well as unanaesthetized mammals (2, 13, 14). Recently we proposed the “cup technique” as a way for studying the efflux of endogenous choline (Ch) from the rat cerebral cortex (4, 5) and to estimate changes in the extracellular concentration of Ch, if we consider the fluid filling the cup as an extension of the extracellular space.
Diverse compounds mimic Alzheimer disease–causing mutations by augmenting Aβ42 production
2004
Increased Abeta42 production has been linked to the development of Alzheimer disease. We now identify a number of compounds that raise Abeta42. Among the more potent Abeta42-raising agents identified are fenofibrate, an antilipidemic agent, and celecoxib, a COX-2-selective NSAID. Many COX-2-selective NSAIDs tested raised Abeta42, including multiple COX-2-selective derivatives of two Abeta42-lowering NSAIDs. Compounds devoid of COX activity and the endogenous isoprenoids FPP and GGPP also raised Abeta42. These compounds seem to target the gamma-secretase complex, increasing gamma-secretase-catalyzed production of Abeta42 in vitro. Short-term in vivo studies show that two Abeta42-raising comp…
Interaction mechanism of endogenous PP2A inhibitor protein ENSA with PP2A
2022
The vast diversity of protein phosphatase 2A (PP2A) holoenzyme composition ensures its multifaceted role in the regulation of cellular growth and signal transduction. In several pathological conditions, such as cancer, PP2A is inhibited by endogenous inhibitor proteins. Several PP2A inhibitor proteins have been identified, one of which is α-endosulfine (ENSA). ENSA inhibits PP2A activity when it is phosphorylated at Ser67 by Greatwall (Gwl) kinase. The role of ENSA in PP2A inhibition is rather well characterized, but knowledge of the mechanism of inhibition is scarce. In this study, we have performed comprehensive structural characterization of ENSA, and its interaction with PP2A A- and var…
Cutting Edge: TGF-β Signaling Is Required for the In Vivo Expansion and Immunosuppressive Capacity of Regulatory CD4+CD25+ T Cells
2004
Abstract Data regarding the role of TGF-β for the in vivo function of regulatory CD4+CD25+ T cells (Treg) are controversial. A transgenic mouse model with impaired TGF-β signaling specifically in T cells was used to assess the role of endogenous TGF-β for the in vivo function of CD4+CD25+ Treg in a murine model of colitis induced by dextran sulfate. Transfer of wild-type, but not transgenic CD4+CD25+ Treg was found to suppress colitis in wild-type mice. In addition, by transferring CFSE-labeled CD4+CD25+ Treg we could demonstrate that endogenous TGF-β promotes the expansion of CD4+CD25+ Treg in vivo. Transgenic mice themselves developed reduced numbers of peripheral CD4+CD25+ Treg and were …
Copper homeostasis influences the circadian clock in Arabidopsis.
2010
Almost every aspect of plant physiology is influenced by diurnal and seasonal environmental cycles which suggests that biochemical oscillations must be a pervasive phenomenon in the underlying molecular organization. The circadian clock is entrained by light and temperature cycles, and controls a wide variety of endogenous processes that enable plants to anticipate the daily periodicity of environmental conditions. Several previous reports suggest a connection between copper (Cu) homeostasis and the circadian clock in different organisms other than plants. However, the nature of the Cu homeostasis influence on chronobiology remains elusive. Cytosolic Cu content could oscillate since Cu regu…