Endothelial dysfunction associated with atherosclerosis has been attributed to alterations in the L-arginine-nitric oxide (NO)-cGMP pathway or an excess of endothelin-1 (ET-1). The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) have shown ameliorate endothelial function. However, physiological basis this observation is largely unknown. We investigated effects Atorvastatin and Simvastatin on pre-proET-1 mRNA expression ET-1 synthesis NO synthase (eNOS) transcript protein...

The cellular redox status can modify the function of NF-κB, whose DNA-binding activity be inhibited by oxidative, nitrosative, and nonphysiological agents such as diamide, iodoacetamide, or N-ethylmaleimide. This inhibitory effect has been proposed to mediated oxidation a conserved cysteine in its domain (Cys62) through unknown biochemical mechanisms. aim this work was identify new oxidative modifications Cys62 involved regulation NF-κB subunit p50. To address problem, we exposed p50, both...

Protein isoprenylation is a post-translational modification essential for the biological activity of G-proteins. Inhibition protein by lovastatin (LOV) induces apoptosis in HL-60 cells, process active cell death characterized internucleosomal degradation genomic DNA. In this article we show that LOV-induced associated with intracellular acidification and activation Na+/H+ antiporter raise pHi which sufficient to prevent or arrest DNA digestion. First, LOV induced decrease was dose-dependent...

Cyclopentenone prostaglandins display anti-inflammatory activities and interfere with the signaling pathway that leads to activation of transcription factor NF-κB. Here we explore possibility NF-κB subunit p50 may be a target for cyclopentenone 15-deoxy-Δ^12,14-prostaglandin J₂(15d-PGJ₂). This prostaglandin inhibited DNA binding ability recombinant in dose-dependent manner. The inhibition required moiety could prevented but not reverted by glutathione...

Protein prenylation with farnesyl or geranylgeranyl moieties is an important posttranslational modification that affects the activity of such diverse proteins as nuclear lamins, yeast mating factor mata, and ras oncogene products. In this article, we show whole retinal cultures incorporate radioactive mevalonic acid into 23-26 kDa one 8 kDa. The former are probably "small" guanine nucleotide-binding regulatory (G proteins) 8-kDa protein gamma subunit well-studied heterotrimeric G...

Abstract The vimentin filament network plays a key role in cell architecture and signalling, as well epithelial–mesenchymal transition. Vimentin C328 is targeted by various oxidative modifications, but its organization not known. Here we show that essential for reorganization response to oxidants electrophiles, required optimal performance expansion, lysosomal distribution aggresome formation. may fulfil these roles through interaction with zinc. In vitro , micromolar zinc protects from...

Abstract The vimentin network displays remarkable plasticity to support basic cellular functions and reorganizes during cell division. Here, we show that in several types filaments redistribute the cortex mitosis, forming a robust framework interwoven with cortical actin affecting its organization. Importantly, intrinsically disordered tail domain of is essential for this redistribution, which allows normal mitotic progression. A tailless mutant forms curly bundles, remain entangled dividing...

Idiopathic pulmonary fibrosis (IPF) is a progressive disease, with median survival of 3–5 years following diagnosis. Lung remodeling by invasive fibroblasts hallmark IPF. In this study, we demonstrate that inhibition vimentin intermediate filaments (VimIFs) decreases the invasiveness IPF and confers protection against in murine model experimental lung injury. Increased expression organization VimIFs contribute to property connection deficient cellular autophagy. Blocking VimIF assembly...

Abstract —Endothelial dysfunction is characterized by an impaired vasodilatory response to endothelial agonists as well alterations in adhesion and coagulation processes. 3-Hydroxy-3-methylglutaryl-CoA reductase inhibitors (statins) have been shown be useful the reversal of dysfunction, effect that may independent reduction cholesterol levels. Both l -arginine–nitric oxide–cGMP endothelin pathways are involved regulation vascular tone. Here, we show basal transcription rate...

Retinal transducin was previously shown to be farnesylated on its gamma subunit. This farnesylation reaction a cysteine residue near the carboxyl terminus is followed by peptidase cleavage at cysteine. Thus modified becomes terminus. It here that free group can methylated an S-adenosyl-L-methionine-dependent methyltransferase associated with rod outer segment membranes. process inhibited S-adenosyl-L-homocysteine and sinefungin. Moreover, synthetic N-acetyl-S-farnesyl-L-cysteine, but not...

Cyclopentenone prostaglandins may interfere with cellular functions by multiple mechanisms. The cyclopentenone 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) has been reported to inhibit the activity of transcription factor AP-1 in several experimental settings. We have explored possibility a direct interaction 15d-PGJ2 proteins. Here we show that covalently modifies c-Jun and directly inhibits DNA binding AP-1. modification occurs both vitro intact cells as detected labeling biotinylated mass...

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTRemoval of the 9-methyl group retinal inhibits signal transduction in visual process. A fourier transform infrared and biochemical investigationUlrich M. Ganter, Eduard D. Schmid, Dolores Perez-Sala, Robert R. Rando, Friedrich SiebertCite this: Biochemistry 1989, 28, 14, 5954–5962Publication Date (Print):July 11, 1989Publication History Published online1 May 2002Published inissue 11 July...

The cyclopentenone 15-deoxy-Δ 12,14 -prostaglandin J 2 (15d-PGJ ) induces cell proliferation and mitogen-activated protein kinase activation. Here, we describe that these effects are mediated by 15d-PGJ -elicited H-Ras We demonstrate this pathway is specific for through the formation of a covalent adduct with Cys-184 H-Ras, but not N-Ras or K-Ras. Mutation C184 inhibited modification activation , whereas serum-elicited stimulation was affected. These results mechanism Ras signaling pathway,...

A new family of fluorescent synthetic molecular probes for nitric oxide sensing based on ortho-hydroxyamino-triarylpyrylium salts is presented.

The intermediate filament protein vimentin constitutes a critical sensor for electrophilic and oxidative stress, which induce extensive reorganization of the cytoskeletal network. Here, we have investigated mechanisms underlying these effects. In vitro, lipids, including 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) 4-hydroxynonenal (HNE), directly bind to vimentin, whereas oxidant diamide induces disulfide bond formation. Mutation single cysteine residue (Cys328) blunts formation reduces...

Cysteine residues can undergo multiple posttranslational modifications with diverse functional consequences, potentially behaving as tunable sensors. The intermediate filament protein vimentin has important implications in pathophysiology, including cancer progression, infection, and fibrosis, maintains a close interplay other cytoskeletal structures, such actin filaments microtubules. We previously showed that the single cysteine, C328, is key target for oxidants electrophiles. Here, we...

Arterial vasodilatation is thought to play a major role in the pathogenesis of systemic hemodynamics and renal disturbances occurring cirrhotic patients. Recent investigations suggest that an increased vascular nitric oxide (NO) production could be implicated this abnormality. The current study assessed whether expression inducible and/or endothelial synthase (iNOS eNOS, respectively) occurs arterial vessels rats. investigation was performed thoracic abdominal aortas mesenteric arteries 10...

Signal transducing G proteins, such as transducin, are prenylated and methylated at carboxyl-terminal cysteine residues. The methylation of transducin occurs by means a membrane bound S-adenosyl methionine-dependent methyltransferase. This methyltransferase accepts the simple modified amino acid N-acetyl-S-farnesyl-L-cysteine (AFC) substrate. that enzyme does not require peptide sequences in putative Moreover, small structural changes AFC unit all lead to molecules incapable being...