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101.
Rocha ME Bandy B Costa CA de Barros MP Pinto AM Bechara EJ 《Free radical research》2000,32(4):343-353
Accumulation of 5-aminolevulinic acid (ALA) is an event characteristic of porphyrias that may contribute to their pathological manifestations. To investigate effects of ALA independent of porphyrin accumulation we treated rats with the methyl ester of succinylacetone, an inhibitor of 5-aminolevulinic acid dehydratase that accumulates in the porphyric-like syndrome hereditary tyrosinemia. Acute 2-day treatment of fasted rats with succinylacetone methyl ester (SAME) promoted a 27% increase in plasma ALA. This increase in plasma ALA was accompanied by augmentation of the level of total nonheme iron in liver (37%) and brain (20%). Mobilization of iron was also indicated by 49% increase in plasma iron and a 77% increase in plasma transferrin saturation. Liver responded with a mild (12%) increase in ferritin. Under these acute conditions, some indications of oxidative stress were evident: a 15% increase in liver reactive protein carbonyls, and a 42% increase in brain subcellular membrane TBARS. Brain also showed a 44% increase in CuZnSOD activity, consistent with observations in treatment with ALA. Overall, the data indicate that SAME promotes ALA-driven changes in iron metabolism that could lead to increased production of free radicals. The findings support other evidence that accumulation of ALA in porphyrias and hereditary tyrosinemia may induce iron-dependent biological damage that contributes to neuropathy and hepatoma. 相似文献
102.
Victoria Schmidt Marlon Sidore Cherine Bechara Jean-Pierre Duneau James N. Sturgis 《生物化学与生物物理学报:生物膜》2019,1861(2):431-440
In this study, we have investigated the lipids surrounding AqpZ, and the effects of a destabilizing mutation W14A (Schmidt and Sturgis, 2017) on lipid protein interactions. In a first approach, we used Styrene Maleic Acid copolymer to prepare AqpZ containing nanodiscs, and these were analyzed for their lipid content, investigating both the lipid head-group and acyl-chain compositions. These results were complemented by native mass spectrometry of purified AqpZ in the presence of lipids, to give insights of variations in lipid binding at the surface of AqpZ. In an effort to gain molecular insights, to aid interpretation of these results, we performed a series of coarse grained molecular dynamics simulations of AqpZ, in mixed lipid membranes, and correlated our observations with the experimental measurements. These various results are then integrated to give a clearer picture of the lipid environment of AqpZ, both in the native membrane, and in lipid nanodiscs. We conclude that AqpZ contains a lipid binding-site, at the interface between the monomers of the tetramer, that is specific for cardiolipin. Almost all the cardiolipin, in AqpZ containing nanodiscs, is probably associated with this site. The SMA 3:1 nanodiscs we obtained contain a rather high proportion of lipid, and in the case of nanodiscs containing AqpZ cardiolipin is depleted. This is possibly because, in the membrane, there is little cardiolipin not associated with binding sites on the surface of the different membrane proteins. Surprisingly, we see no evidence for lipid sorting based on acyl chain length, even in the presence of a large hydrophobic mismatch, suggesting that conformational restrictions are energetically less costly than lipid sorting. 相似文献
103.
Thomas Maurin Mireille Melko Sabiha Abekhoukh Olfa Khalfallah Laetitia Davidovic Marielle Jarjat Simona D'Antoni Maria Vincenza Catania Hervé Moine Elias Bechara Barbara Bardoni 《Nucleic acids research》2015,43(17):8540-8550
Fragile X syndrome (FXS), the most common form of inherited intellectual disability, is caused by the silencing of the FMR1 gene encoding an RNA-binding protein (FMRP) mainly involved in translational control. We characterized the interaction between FMRP and the mRNA of GRK4, a member of the guanine nucleotide-binding protein (G protein)-coupled receptor kinase super-family, both in vitro and in vivo. While the mRNA level of GRK4 is unchanged in the absence or in the presence of FMRP in different regions of the brain, GRK4 protein level is increased in Fmr1-null cerebellum, suggesting that FMRP negatively modulates the expression of GRK4 at the translational level in this brain region. The C-terminal region of FMRP interacts with a domain of GRK4 mRNA, that we called G4RIF, that is folded in four stem loops. The SL1 stem loop of G4RIF is protected by FMRP and is part of the S1/S2 sub-domain that directs translation repression of a reporter mRNA by FMRP. These data confirm the role of the G4RIF/FMRP complex in translational regulation. Considering the role of GRK4 in GABAB receptors desensitization, our results suggest that an increased GRK4 levels in FXS might contribute to cerebellum-dependent phenotypes through a deregulated desensitization of GABAB receptors. 相似文献
104.
Michael Sand Samuel Uecker Falk G Bechara Marcos Gelos Daniel Sand Till H Wiese Benno Mann 《International Seminars in Surgical Oncology : ISSO》2007,4(1):15
Medullary thyroid carcinomas (MTC) constitute about 5 to 7 % of thyroid neoplasms. They originate from parafollicular C-cells which can secrete adrenocorticotropic hormone (ACTH) and/or corticotropin-releasing factor (CRF) in abnormally high concentrations, potentially causing paraneoplastic Cushing's Syndrome (CS).We report on a 42-year-old male patient with a ten year history of metastatic medullary thyroid carcinoma suffering from paraneoplastic Cushing's Syndrome caused by ectopic hypersecretion of ACTH and a simultaneous Cortisol producing adrenal metastasis. 相似文献
105.
106.
The Gambler’s Fallacy Is Associated with Weak Affective Decision Making but Strong Cognitive Ability
Gui Xue Qinghua He Xuemei Lei Chunhui Chen Yuyun Liu Chuansheng Chen Zhong-Lin Lu Qi Dong Antoine Bechara 《PloS one》2012,7(10)
Humans demonstrate an inherent bias towards making maladaptive decisions, as shown by a phenomenon known as the gambler’s fallacy (GF). The GF has been traditionally considered as a heuristic bias supported by the fast and automatic intuition system, which can be overcome by the reasoning system. The present study examined an intriguing hypothesis, based on emerging evidence from neuroscience research, that the GF might be attributed to a weak affective but strong cognitive decision making mechanism. With data from a large sample of college students, we found that individuals’ use of the GF strategy was positively correlated with their general intelligence and executive function, such as working memory and conflict resolution, but negatively correlated with their affective decision making capacities, as measured by the Iowa Gambling Task. Our result provides a novel insight into the mechanisms underlying the GF, which highlights the significant role of affective mechanisms in adaptive decision-making. 相似文献
107.
Marilene Demasi Cristine A. Costa Carlos Pascual Susana Llesw Etelvino J. H. Bechara 《Free radical research》1997,26(3):235-243
The heme precursor 5-aminolevulinic acid (ALA), acting as a prooxidant, has been proposed to underlie the clinical manifestations of various porphyric disorders. Accordingly, ALA-generated oxyradicals where shown to cause oxidative lesions in biomolecules and isolated cell organelles and to release iron from ferritin. In rats, administered ALA triggered oxidative stress in liver, brain and red muscles. We now study the correlation between the plasma antioxidant capacity and tissue oxidative damage, after acute (one and two doses) and prolonged (eight doses) ALA treatment of rats (one dose of ALA = 40 mg/kg body weight). The in situ spontaneous chemiluminescence intensity increased 5-fold in brain, 50% in liver and 4-fold in soleus muscle upon two dose-treatment, indicating tissue response to oxidative injury by ALA. Chemiluminescence reached the highest intensity after one or two doses of ALA and decreased after eight doses in all tissues. The plasma trapping capacity, evaluated by the luminol/2-amidinopropane system, gave a parallel response: maximum values after two doses and decreased values after prolonged treatment. After eight doses, the ALA concentration was found to be 3-fold above the normal value in plasma, 48% higher in liver and 38% higher in total brain. These data indicate that the plasma antioxidant system responds to ALA treatment and is correlated with tissue chemiluminescence. In vitro studies showed that ALA does not interfere with the antioxidant plasma capacity, neither promoting oxidation of plasma elements nor binding to plasma proteins. 相似文献
108.
alpha 1-Proteinase inhibitors (alpha 1-PIs) are members of the serpin
superfamily of proteinase inhibitors, and are important in the maintenance
of homeostasis in a wide variety of animal taxa. Previous studies have
shown that in mice (genus Mus), evolution of alpha 1-PIs is characterized
by gene amplification, region-specific concerted evolution, and rapid
accumulation of amino acid substitutions. The latter occurs primarily in
the reactive center, which is the region of the alpha 1-PI molecule that
determines the inhibitor's specificity for target proteinases. The P1
residue within the reactive center, which is methionine in so-called
orthodox alpha 1-PIs and an amino acid other than methionine in unorthodox
alpha 1-PIs, is a primary determinant of inhibitor specificity. In the
present study, we find that the expression of mRNAs encoding unorthodox
alpha 1-PIs is polymorphic within Mus species, i.e., among individuals or
inbred strains. This is in striking contrast to mRNAs that encode orthodox
alpha 1-PIs, whose concentrations are relatively invariant. The
intraspecies variations in mRNA expression represent polymorphisms in the
structure of the alpha 1- PI gene family. The results, taken together with
previously described aspects of alpha 1-PI evolution, indicate that the
dissimilar levels of polymorphism exhibited by orthodox and unorthodox
alpha 1-PIs, which likely have distinct physiological functions, may
reflect different levels of selective constraint. The significance of this
finding to the evolution of gene families is discussed.
相似文献
109.
110.
Marcelo D Bechara Márcio C Moretzsohn Darío A Palmieri Jomar P Monteiro Maurício BacciJr Joaquim MartinsJr José FM Valls Catalina R Lopes Marcos A Gimenes 《BMC plant biology》2010,10(1):255