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21.
H Blum J C Salerno M A Cusanovich 《Biochemical and biophysical research communications》1978,84(4):1125-1128
EPR spectra of oxidized HiPIP demonstrate two kinds of temperature dependent changes which can be analyzed in terms of an excited state at 142 ± 10cm?1 and a second excited state at 490 ± 100cm?1. These states represent further verification of antiferromagnetic exchange among the 4 irons in this tetranuclear cluster, with a value for the coupling constant of J = ?44cm?1. Aside from resonance Raman spectroscopic results, this is the first report of a ladder of excited states predicted for exchange coupled ions. 相似文献
22.
Two distinct ferredosin-type iron-sulfur centers (designated as Centers S-1 and S-2) are present in the soulble succinate dehydrogenase in approximately equivalent concentrations to that of bound flavin. Both Centers S-1 and S-2 exhibit electron paramagnetic resonance absorbance in the reduced state at the same magnetic field (gz = 2.03, gy = 1.93, and gx = 1.91) with similar line shape. Center S-2 is reducible only chemically with dithionite and remains oxidized under physiological conditions. Thus, its functional role is unknown; however, thermodynamic and EPR characterization of this iron-sulfur center has revealed important molecular events related to this dehydrogenase. The midpoint potentials of Centers S-1 and S-2 determined in the soluble succinate dehydrogenase preparations are -5 +/- 15 mV and -400 +/- 15 mV, respectively, while corresponding midpoint potentials determined in particulate preparations, such as succinate-cytochrome c reductase or succinate-ubiquinone reductase, are 0 +/- 15 mV and -260 +/- 15 mV. Reconstitution of soluble succinate dehydrogenase with the cytochrome b-c1 complex is accompanied by a reversion of the Center S-I midpoint from -400 +/- 15 mV to -250 +/- 15 mV with a concomitant restoration of antimycin A-sensitive succinate-cytochrome c reductase activity. There observations indicate that, during the reconstitution process, Center S-I is restored to its original molecular environment. In the reconstitutively active succinate dehydrogenase, the relaxation time of Center S-2 is much shorter than that of S-1, thus Center S-2 spectra are well discernible only below 20 K (at 1 milliwatt of power), while the resonance absorbance of Center S-1 is detectable at higher temperatures and readily saturates below 15 K. Over a wide temperature range the power saturation of Center S-1 resonance absorbance is relieved by Center S-2 in the paramagnetic state, and the Center S-2 central resonance absorbance is broadened by Center S-1 spins, due to a spin-spin interaction between these centers. These observations indicate an adjacent location of these centers in the enzyme molecule. In reconstitutively inactive enzymes, subtle modification of the enzyme structure appears to shift the temperature dependence of Center S-2 relaxation to the higher temperature. Thus the EPR signals of Center S-2 are also detectable at higher temperature. In this system a splitting of the central peak of the Center S-2 spectrum due to spin-spin interaction was observed at extremely low temperatures, while this was not observed in reconstitutively active enzymes or in paritculate preparations. This spin-spin interaction phenomena of inactive enzymes disappeared upon chemical reactivation with concomitant appearance of the reconstitutive activity. These observations provide a close correlation between the molecular integrity of the enzyme and its physiological function. 相似文献
23.
Cholecystokinin-8 like immunoreactivity (CCK-8 IR) was measured in different brain regions of rats with experimental liver cirrhosis. A statistically significant reduction of CCK-8 content was observed in the hypothalamus of cirrhotic rats. No significant modification of brain CCK fractionation pattern was observed in treated animals as compared to controls. The decrease of CCK-8 IR parallels the recently reported hypothalamic depletion of beta endorphin in cirrhotic rats confirming that central neuropeptides are affected by chronic liver failure. 相似文献
24.
J. David Lambeth David W. Seybert Jack R. Lancaster Jr. John C. Salerno Henry Kamin 《Molecular and cellular biochemistry》1982,45(1):13-31
Summary The flavoprotein NADPH-adrenodoxin reductase and the iron sulfur protein adrenodoxin function as a short electron transport chain which donates electrons one-at-a-time to adrenal cortex mitochondrial cytochromes P-450. The soluble adrenodoxin acts as a mobile one-electron shuttle, forming a complex first with NADPH-reduced adrenodoxin reductase from which it accepts an electron, then dissociating, and finally reassociating with and donating an electron to the membrane-bound cytochrome P-450 (Fig. 9). Dissociation and reassociation with flavoprotein then allows a second cycle of electron transfers. A complex set of factors govern the sequential protein-protein interactions which comprise this adrenodoxin shuttle mechanism; among these factors, reduction of the iron sulfur center by the flavin weakens the adrenodoxinadrenodoxin reductase interaction, thus promoting dissociation of this complex to yield free reduced adrenodoxin. Substrate (cholesterol) binding to cytochrome P-450scc both promotes the binding of the free adrenodoxin to the cytochrome, and alters the oxidation-reduction potential of the heme so as to favor reduction by adrenodoxin. The cholesterol binding site on cytochrome P-450scc appears to be in direct communication with the hydrophobic phospholipid milieu in which this substrate is dissolved. Specific effects of both phospholipid headgroups and fatty acyl side-chains regulate the interaction of cholesterol with its binding side. Cardiolipin is an extremely potent positive effector for cholesterol binding, and evidence supports the existence of a specific effector lipid binding site on cytochrome P.450scc to which this phospho-lipid binds. 相似文献
25.
Luana Lionetto Martina Ulivieri Matilde Capi Donatella De Bernardini Francesco Fazio Andrea Petrucca Leda Marina Pomes Ottavia De Luca Giovanna Gentile Barbara Casolla Martina Curto Gerardo Salerno Serena Schillizzi Maria Simona Torre Iolanda Santino Monica Rocco Paolo Marchetti Antonio Aceti Marina Borro 《生物化学与生物物理学报:疾病的分子基础》2021,1867(3):166042
Immune dysregulation is a hallmark of patients infected by SARS-CoV2 and the balance between immune reactivity and tolerance is a key determinant of all stages of infection, including the excessive inflammatory state causing the acute respiratory distress syndrome. The kynurenine pathway (KP) of tryptophan (Trp) metabolism is activated by pro-inflammatory cytokines and drives mechanisms of immune tolerance. We examined the state of activation of the KP by measuring the Kyn:Trp ratio in the serum of healthy subjects (n = 239), and SARS-CoV2-negative (n = 305) and -positive patients (n = 89). Patients were recruited at the Emergency Room of St. Andrea Hospital (Rome, Italy). Kyn and Trp serum levels were assessed by HPLC/MS-MS. Compared to healthy controls, both SARS-CoV2-negative and -positive patients showed an increase in the Kyn:Trp ratio. The increase was larger in SARS-CoV2-positive patients, with a significant difference between SARS-CoV2-positive and -negative patients. In addition, the increase was more prominent in males, and positively correlated with age and severity of SARS-CoV2 infection, categorized as follows: 1 = no need for intensive care unit (ICU); 2 ≤ 3 weeks spent in ICU; 3 ≥ 3 weeks spent in ICU; and 4 = death. The highest Kyn:Trp values were found in SARS-CoV2-positive patients with severe lymphopenia. These findings suggest that the Kyn:Trp ratio reflects the level of inflammation associated with SARS-CoV2 infection, and, therefore, might represent a valuable biomarker for therapeutic intervention. 相似文献
26.
Giovanni Mantovani Antonio Macciò Clelia Madeddu Loredana Mura Giulia Gramignano Maria Rita Lusso 《Free radical research》2013,47(2):213-223
In the present study we tested the ability of different antioxidant agents, used alone or in combination, to reduce the reactive oxygen species (ROS) levels and to increase the glutathione peroxidase (GPx) activity. Moreover, we tested the ability of such antioxidant agents to reduce the serum levels of proinflammatory cytokines IL-6 and TNF f . Fifty-six advanced stage cancer patients with tumors at different sites were included in the study: they were mainly stage III (12.5%) and stage IV (82.1%). The study was divided into two phases. In the 1 st phase 28 patients were divided into five groups and a single different antioxidant agent was administered to each group. The selected antioxidant agents were: alpha lipoic acid or carboxycysteine-lysine salt, amifostine, reduced glutathione, vitamin A plus vitamin E plus Vitamin C. In the 2 nd phase of the study 28 patients were divided into five groups and a combination of two different antioxidant agents was administered to each group. The antioxidant treatment was administered for 10 consecutive days. The patients were studied at baseline and after antioxidant treatment. Our results show that all single antioxidants tested were effective in reducing the ROS levels and three of them in increasing GPx activity, too. Among the combinations of antioxidant agents, three were effective in reducing ROS, while three were effective in increasing GPx activity (arm 4 was effective in both instances). Comprehensively, the "antioxidant treatment" was found to be effective both on ROS levels and GPx activity. Moreover, the antioxidant treatment was able to reduce serum levels of IL-6 and TNF f . Furthermore, a correlation was shown between the Eastern Cooperative Oncology Group Performance Status of patients and blood levels of ROS, GPx activity, serum levels of proinflammatory cytokines. 相似文献
27.
The complex history of the Mediterranean region illustrates how ancient and recent phenomena are closely associated with species distribution and the creation of phylogeographic divisions within Mediterranean flora. A good model to explore the genetic consequences of fragmentation can be found in Centaurea cineraria and its close relatives. We applied simple sequence repeat molecular markers to a dense population sampling throughout the distribution area of all C. cineraria taxa to study how fragmentation has altered the genetic structure and distribution of C. cineraria. The average gene diversity (He) was 0.286, and the average allelic richness (Ar) was 3.65 and ranged from 2.15 (C. gymnocarpa) to 5.25 (C. busambarensis). The FIS averaged a relatively high 0.223, ranging from ? 0.724 in C. aeolica subsp. aeolica to 0.589 in C. leucadea. Our results indicate that habitat fragmentation over several generations reduced heterozygosity due to random genetic drift in populations of C. cineraria. This heterozygosity erosion becomes more severe when the inbreeding coefficient is positive and the outcrossing rates show a significant increase. The results observed for outcrossing rates and inbreeding coefficient could also indirectly support the possibility of disrupted gene flow or mating pattern changes in fragmented C. cineraria populations. 相似文献
28.
Loredana Cappellacci Kamal N. Tiwari John A. Montgomery John A. Secrist III 《Nucleosides, nucleotides & nucleic acids》2013,32(4-5):613-614
Abstract 1-O-Acetyl-2-deoxy-3,5-di-O-toluoyl-4-thio-d-erythro-pentofuranose and 2-deoxy-1,3,5-tri-O-acetyl-4-thio-l-threo-pentofuranose were coupled with 5-azacytosine to obtain α and β anomers of nucleosides. 相似文献
29.
Gea Guerriero Lucia Silvestrini Michael Obersriebnig Marco Salerno Dietmar Pum Joseph Strauss 《PloS one》2013,8(11)
The fungal cell wall constitutes an important target for the development of antifungal drugs, because of its central role in morphogenesis, development and determination of fungal-specific molecular features. Fungal walls are characterized by a network of interconnected glycoproteins and polysaccharides, namely α-, β-glucans and chitin. Cell walls promptly and dynamically respond to environmental stimuli by a signaling mechanism, which triggers, among other responses, modulations in wall biosynthetic genes’ expression. Despite the absence of cellulose in the wall of the model filamentous fungus Aspergillus nidulans, we found in this study that fungal growth, spore germination and morphology are affected by the addition of the cellulose synthase inhibitor dichlobenil. Expression analysis of selected genes putatively involved in cell wall biosynthesis, carried out at different time points of drug exposure (i.e. 0, 1, 3, 6 and 24 h), revealed increased expression for the putative mixed linkage β-1,3;1,4 glucan synthase celA together with the β-1,3-glucan synthase fksA and the Rho-related GTPase rhoA. We also compared these data with the response to Congo Red, a known plant/fungal drug affecting both chitin and cellulose biosynthesis. The two drugs exerted different effects at the cell wall level, as shown by gene expression analysis and the ultrastructural features observed through atomic force microscopy and scanning electron microscopy. Although the concentration of dichlobenil required to affect growth of A. nidulans is approximately 10-fold higher than that required to inhibit plant cellulose biosynthesis, our work for the first time demonstrates that a cellulose biosynthesis inhibitor affects fungal growth, changes fungal morphology and expression of genes connected to fungal cell wall biosynthesis. 相似文献
30.
Jae Young So Amanda K. Smolarek David M. Salerno Hubert Maehr Milan Uskokovic Fang Liu Nanjoo Suh 《PloS one》2013,8(1)