1,721,057 research outputs found
Methylmercury injury to CNS: mitochondria at the core of the matter?
Full text linkMethyl-mercury (MeHg) is one of the most hazardous environmental pollutants of great concern to public health and regulatory agencies because of its primary toxicity to the human central nervous system. The major source of MeHg exposure to the general population is through consumption of contaminated fish and other food products. MeHg, absorbed from the gastrointestinal tract, is easily transported across the blood-brain barrier (BBB). Cysteine-facilitated transport of MeHg into the brain has been demonstrated, and in particular a neutral amino acid transport system capable of mediating MeHg-cysteine uptake has been identified in astrocytes where MeHg accumulation induces cell swelling and inhibition of glutamate uptake. Elevation of glutamate levels in the extracellular space may, in turn, trigger or accelerate processes of excitotoxic neuro degeneration. The rising of extracellular glutamate levels is responsible for the sustained activation of glutamate receptors, hence enhancing Na+ influx and Ca2+ release from intracellular organelles that may trigger a biochemical cascade which promotes the reactive oxygen species (ROS) production. In this scenario, mitochondria may play a crucial role, as these organelles act as a buffer against cytosolic calcium and mediate ROS formation in cells. Herein, we summarize studies providing insights into the molecular and cellular mechanisms involved in MeHg-induced neuro degeneration with particular focus on the role of astrocytes and mitochondria. Indeed, mitochondria may be supposed to lie at the crossroads of a network of events (microtubule disorganization, Ca2+ dyshomeostasis, ROS generation) leading to neuro degeneration, although it is difficult to establish the upstream mechanisms and downstream effectors in this cascade of event
Protein phosphatase(s) acting on cAMP dependent phosphoproteins in bovine heart mitochondria
No full textEthanol-induced changes of intracellular thiol compartmentation and protein redox status in the rat liver:effect of tauroursodeoxycolate
No full textBACKGROUND/AIMS:
Ethanol impairs cellular antioxidant defense and protein metabolism. Hydrophilic bile acids are protective against ethanol-induced cytotoxicity. This study investigated the compartmentation of intracellular thiol and protein redox status after acute ethanol intoxication in the liver and the effect of tauroursodeoxycholate pretreatment.
METHODS:
The concentrations of total glutathione, glutathione bound to proteins, sulfhydryl proteins, carbonyl proteins and malondialdehyde were measured in hepatic cytosol, mitochondria and nuclei after oral administration of 25% ethanol (4 g/kg) or isocaloric carbohydrate solution to rats. The metabolisms of ethanol and acetaldehyde were investigated by giving 4-methylpyrazole (1 mmol/kg i.p.) or cyanamide (15 mg/kg i.p.) 1 h prior to ethanol ingestion. One group of rats received tauroursodeoxycholate (12 mg/kg p.os) 1 h before ethanol ingestion.
RESULTS:
Ethanol significantly decreased the glutathione concentrations. Significant increases in glutathione bound to proteins, carbonyl protein and malondialdehyde concentrations were also noted, especially at the mitochondrial level. Enhanced carbonyl protein formation was also observed (p < 0.01). The inhibition of acetaldehyde metabolism, but not ethanol metabolism, exaggerated the alterations produced by ethanol. Pretreatment with tauroursodeoxycholate significantly reduced lipid and protein oxidation, particularly in mitochondria. By contrast, no changes were observed in glutathione content and compartmentation.
CONCLUSIONS:
Ethanol intoxication differentially impairs thiol and protein redox status in the subcellular fractions of rat liver. These alterations seem dependent on acetaldehyde rather than ethanol. Tauroursodeoxycholate administration protects proteins and lipids from ethanol-induced oxidative damage without influencing the glutathione content and compartmentation
CAMP RESPONSE ELEMENT-BINDING PROTEIN (CREB) IS IMPORTED INTO MITOCHONDRIA AND PROMOTES PROTEIN SYNTHESIS
No full textThe cAMP response element-binding protein (CREB) is a ubiquitous transcription factor in the higher eukaryotes that, once phosphorylated, promotes transcription of cAMP response element-regulated genes. We have studied the mitochondrial import of CREB and its effect on the expression of mtDNA-encoded proteins. [(35)S]Methionine-labelled CREB, synthesized in vitro in the Rabbit Reticulocyte Lysate system using a construct of the human cDNA, was imported into the matrix of isolated rat liver mitochondria by a membrane potential and TOM complex-dependent process. The imported CREB caused cAMP-dependent promotion of the synthesis of mitochondrially encoded subunits of oxidative phosphorylation enzyme complexes. Thus, CREB moves from the cytosol to mitochondria, in addition to the nucleus, and, when phosphorylated by cAMP-dependent protein kinase, promotes the expression of mitochondrial genes
Ovarian Cancer: A Landscape of Mitochondria with Emphasis on Mitochondrial Dynamics
Full text linkOvarian cancer (OC) represents the main cause of death from gynecological malignancies in western countries. Altered cellular and mitochondrial metabolism are considered hallmarks in cancer disease. Several mitochondrial aspects have been found altered in OC, such as the oxidative phosphorylation system, oxidative stress and mitochondrial dynamics. Mitochondrial dynamics includes cristae remodeling, fusion, and fission processes forming a dynamic mitochondrial network. Alteration of mitochondrial dynamics is associated with metabolic change in tumour development and, in particular, the mitochondrial shaping proteins appear also to be responsible for the chemosensitivity and/or chemoresistance in OC. In this review a focus on the mitochondrial dynamics in OC cells is presented
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Characterization of the kinetic and substrate of mitochondrial cAMP-dependent protein kinase
No full textCyclic adenosine monophosphate-dependent phosphorylation of mammalian mitochondrial proteins: Enzyme and substrate characterization and functional role
No full textA study is presented on cyclic adenosine monophosphate- (cAMP-) dependent phosphorylation of mammalian mitochondrial proteins. Immunodetection with specific antibodies reveals the presence of the catalytic and the regulatory subunits of cAMP-dependent protein kinase (PKA) in the inner membrane and matrix of bovine heart mitochondria. The mitochondrial cAMP-dependent protein kinase phosphorylates mitochondrial proteins of 29, 18, and 6.5 kDa. With added histone as substrate, PKA exhibits affinities for ATP and cAMP and pH optimum comparable to those of the cytosolic PKA. Among the mitochondrial proteins phosphorylated by PKA, one is the nuclear-encoded (NDUFS4 gene) 18 kDa subunit of complex I, which has phosphorylation consensus sites in the C terminus and in the presequence. cAMP promotes phosphorylation of the 18 kDa subunit of complex I in myoblasts in culture and in their isolated mitoplast fraction. In both cases cAMP-dependent phosphorylation of the 18 kDa subunit of complex I is accompanied by enhancement of the activity of the complex. These results, and the finding of mutations in the NDUFS4,gene in patients with complex I deficiency, provide evidence showing, that cAMP-dependent phosphorylation of the 18 kDa subunit of complex I plays a major role in the control of the mitochondrial respiratory activity
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