bluuebunny/crossref_metadata_2025_split huggingface dataset:
Biogenic 4‐hydroxy‐2‐nonenal activates transcription factor AP‐1 but not NF‐κB in cells of the macrophage lineage
Authors: Camandola Simonetta , Scavazza Antonella , Leonarduzzi Gabriella , Biasi Fiorella , Chiarpotto Elena , Azzi Angelo , Poli Giuseppe 
Published: December 2008

AbstractA large spectrum of pro‐oxidant agents, including molecules with lipoperoxidative effect, can modulate gene expression through modification of the DNA binding activity of the transcription factors activator protein 1 (AP‐1) and nuclear factor kappa B (NF‐κB). In this study the effect on these redox‐sensitive factors by 4‐hydroxy‐2‐nonenal (HNE), a major aldehydic product of lipid peroxidation, was examined in two cell lines of the macrophage type. Incubation in the presence of μM concentrations of the aldehyde led to a rapid increase of AP‐1 binding with a transient maximum 30 min from HNE addition to the culture medium in both cell lines. On the contrary, HNE did not stimulate nuclear translocation of NF‐κB. The diverging effect of HNE on the two transcription factors is likely related to the demonstrated differential activation pathway of AP‐1 and NF‐κB in macrophages. The HNE‐induced activation of AP‐1 suggests the aldehyde's involvement in the regulatory mechanisms of cell proliferation and differentiation.
Polyphenols produced during red wine ageing
Authors: Brouillard R. , George F. , Fougerousse A. 
Published: December 2008

AbstractOver the past few years, it has been accepted that a moderate red wine consumption is a factor beneficial to human health. Indeed, people of France and Italy, the two major wine‐producing European countries, eat a lot of fatty foods but suffer less from fatal heart strokes than people in North‐America or in the northern regions of Europe, where wine is not consumed on a regular basis. For a time, ethanol was thought to be the ‘good’ chemical species hiding behind what is known as the ‘French paradox’. Researchers now have turned their investigations towards a family of natural substances called ‘polyphenols’, which are only found in plants and are abundant in grapes. It is well known that these molecules behave as radical scavengers and antioxidants, and it has been demonstrated that they can protect cholesterol in the LDL species from oxidation, a process thought to be at the origin of many fatal heart attacks. However, taken one by one, it remains difficult to demonstrate which are the best polyphenols as far as their antioxidant activities are concerned. The main obstacle in that kind of research is not the design of the chemical and biological tests themselves, but surprisingly enough, the limited access to chemically pure and structurally elucidated polyphenolic compounds. In this article, particular attention will be paid to polyphenols of red wine made from Vitis vinifera cultivars. With respect to the ‘French paradox’, we address the following question: are wine polyphenolic compounds identical to those found in grapes (skin, pulp and seed), or are there biochemical modifications specifically taking place on the native flavonoids when a wine ages? Indeed, structural changes occur during wine conservation, and one of the most studied of those changes concerns red wine colour evolution, called ‘wine ageing’. As a wine ages, it has been demonstrated that the initially present grape pigments slowly turn into new more stable red pigments. That phenomenon goes on for weeks, months and years. Since grape and wine polyphenols are chemically distinct, their antioxidant activities cannot be the same. So, eating grapes might well lead to beneficial effects on human health, due to the variety and sometimes large amounts of their polyphenolic content. However, epidemiological surveys have focused on wines, not on grapes…
α‐tocopherol protects against expression of adhesion molecules on neutrophils and endothelial cells
Authors: Yoshikawa Toshikazu , Yoshida Norimasa , Manabe Hiroki , Terasawa Yoshimitsu , Takemura Toshiki , Kondo Motoharu 
Published: December 2008

AbstractLeukocyte–endothelial cell interactions, which are mediated by various adhesion molecules, are a crucial event in inflammatory reactions including atherosclerosis. α‐tocopherol (α‐Toc) has been used for therapy of vascular diseases because of its antioxidant activity. However, the effect of α‐Toc on inflammatory reactions has not been investigated very well. In the present study, we examined the effect of α‐Toc on expression of adhesion molecules on human neutrophils and human umbilical vein endothelial cells (HUVEC). Expression of CD11a, CD11b and CD18 on neutrophils was assessed by immunofluorescence flow cytometry 30 min after the stimulation of neutrophils with 10−7 M platelet‐activating factor (PAF). Surface expression of intercellular adhesion molecule‐1 (ICAM‐1) and vascular cell adhesion molecule‐1 (VCAM‐1) on HUVEC was evaluated by enzyme immunoassay 8 h after the incubation of HUVEC with IL‐1β (20 U/ml). PAF induced upregulation of CD11b and CD18 on neutrophils and IL‐1β increased surface expression of ICAM‐1 and VCAM‐1 on HUVEC. Coincubation of neutrophils with α‐Toc and pretreatment of HUVEC with α‐Toc significantly reduced PAF‐induced CD11b/CD18 expression and IL‐1β‐induced upregulation of ICAM‐1 and VCAM‐1, respectively. These findings indicate that α‐Toc may work as an anti‐inflammatory agent through inhibiting neutrophil–endothelial cell adhesive reactions.
Inhibition of NF‐κB transcriptional activity by α‐tocopheryl succinate
Authors: Nakamura Tetsuya , Goto Masaki , Matsumoto Akira , Tanaka Isao 
Published: December 2008

AbstractThe role of vitamin E in cell regulation in addition to its function as an antioxidant has attracted attention. The effects of α‐tocopherol (T) and α‐tocopheryl succinate (TS) on transcriptional activation of the tumor necrosis factor alpha (TNF‐α ) gene and nuclear factor kappa B (NF‐κ B) activation were examined. Two stable transformants were used: TR‐1 cells derived from THP‐1 cells transfected with a vector contains the human TNF‐α promoter (1.4‐kb) joined to the human placental alkaline phosphatase (PLAP) coding sequence, and B164 cells derived from the same cell line but carrying the vector containing the human β‐actin promoter (4.3‐kb) as a control.The transfectants were cultured in the presence of TS, followed by stimulation with lipopolysaccharide (LPS). After stimulation, PLAP activity secreted into the culture medium was measured. TS reduced TNF‐α transcriptional activity in a concentration‐dependent manner, while no effect was observed on that of the β‐actin promoter.Gel shift assay revealed that THP‐1 cells pretreated with TS and then with LPS showed inhibition of NF‐κ B activity by 43% at 50 μM versus the TS‐untreated group. Since TS did not affect activator protein‐1 (AP‐1) activity under the same conditions, the inhibitory effect of TS on NF‐κ B activation might be specific. However, T had no effect on the results of the gel shift assay.Vitamin E transportation was analyzed by simultaneous determination of vitamin E and its derivatives using HPLC. The vitamin E recovered from culture pellets showed almost the same amounts of T and TS transferred and was recovered in unchanged form. These observations indicated that TS inhibited NF‐κ B activation and/or translocation to the nuclei in its unchanged form under the culture conditions used here.These results suggested that vitamin E is involved in signal transduction via an effect distinct from its antioxidant function. To explain the lack of activity with T, it remains to be clarified whether physiological incorporation of T occurred.
Evidence for A1and A2Badenosine receptors in baby hamster kidney (BHK) cells
Authors: Mittal Rashmi A. , Tan Chee‐Hong , Khoo Hoon‐Eng 
Published: December 2008

AbstractAdenosine is known to produce biphasic effects in the renal tissues via adenosine receptors. However, the presence of more than one subtype of adenosine receptor on a type of kidney cell or tissue has not been conclusively demonstrated. To address this issue, we investigated the presence of A1and A2adenosine receptors in baby hamster kidney (BHK) cells by use of radioligand binding and the reverse transcription‐polymerase chain reaction. Ligand binding studies with (3H)‐DPCPX revealed a single class of binding site with a KDof 9.2 ± 2.0 nM, a Bmaxof 1.7 ± 0.2 pmol/mg protein and a pharmacological profile characteristic of A1adenosine receptor on the BHK cell membrane. As the presence of A2adenosine receptors could not be conclusively determined by ligand binding studies, the more sensitive method of RT‐PCR was employed. The presence of A1and A2Badenosine receptors was detected by RT‐PCR with specific primers and the subsequent sequencing of the resultant amplification product. The sequences obtained were 75–90% homologous to the respective adenosine receptor mRNA of rat, mouse and human.
Singlet oxygen scavenging by α‐tocopherol and β‐carotene: Kinetic studies in phospholipid membranes and ethanol solution
Authors: Fukuzawa Kenji , Inokami Yasuki , Tokumura Akira , Terao Junji , Suzuki Asahi 
Published: December 2008

AbstractThe rate constants (ks of 1O2 scavenging for α‐tocopherol (α‐Toc) and β‐carotene (β‐Car) were measured in liposome membranes, and compared with those in EtOH solution. 1O2 was site‐specifically generated by photoirradiation using two photosensitizers, water‐soluble Rose bengal (RB) and lipid‐soluble 12‐(1‐pyrene)‐dodecanoic acid (PDA). The ks value for β‐Car in EtOH solution was 1.3 × 1010 M−1 s−1, which was 36 times that for α‐Toc (3.6 × 108 M−1 s−1), but there was no difference between their ks values in liposomes (1.8 × 107 M−1 s−1 for β‐Car and 1.2 × 107 M−1 s−1 for α‐Toc). In the liposomes, the ks value for α‐Toc was affected by the membrane site where 1O2 was generated, which depended on the localization of the photosensitizer, being high at the membrane surface in the RB‐system and low in the inner region of the membrane in the PDA‐system. In contrast, the ks value for β‐Car was not affected by the 1O2‐generating site. These differences were supposed to be caused by differences in the relative concentrations of 1O2 and active sites of α‐Toc and β‐Car in the membranes. α‐Toc and β‐Car inhibited 1O2‐dependent peroxidation of egg yolk phosphatidylcholine (egg PC). The concentrations of α‐Toc required for 50% inhibition of lipid peroxidation (IC50) were higher than those of β‐Car, being more than 6 times higher in EtOH solution and less than 2 times higher in liposomes. The ratio of the antioxidant activity of β‐Car to that of α‐Toc was more in EtOH solution than in liposomes, and was well correlated with the ratio of their 1O2 scavenging rate constants.
Effect of supplementation with vitamin E on LDL oxidizability and prevention of atherosclerosis
Authors: Suzukawa Michio , Ayaori Makoto , Shige Hideki , Hisada Tetsuya , Ishikawa Toshitsugu , Nakamura Haruo 
Published: December 2008

AbstractSupplementation of LDL with vitamin E is thought to protect LDL from oxidative modification and prevent the development of atherosclerosis. Large epidemiological studies have revealed that vitamin E levels in plasma are inversely correlated to the incidence of coronary heart disease. Double‐blind placebo‐controlled trials have reported that supplementation with vitamin E decreases the incidence of coronary events in coronary heart disease (CHD) patients. However, it is not clear how high a dose of vitamin E is needed to prevent formation of atherosclerosis. In animal studies, a diet containing 0.125% vitamin E increased its levels in plasma two‐fold and prevented formation of early atherosclerotic lesions in the thoracic aorta of hypercholesterolemic rabbits. Dose‐response studies in humans have reported that 400 IU/day vitamin E increased its levels in plasma two‐fold and prolonged the lag time before LDL oxidation. It has been reported that oxidizability of LDL was correlated to the atherosclerotic score of coronary angiography in CHD patients. About 400 IU/day vitamin E, which increases its levels two‐fold and prolongs sufficiently the lag time before LDL oxidation, might be beneficial in decreasing the individual risk of CHD.
Aging and oxidative stress in neurodegeneration
Authors: Urano Shiro , Sato Yuko , Otonari Tomoyuki , Makabe Shinobu , Suzuki Shozo , Ogata Masahiro , Endo Toyoshige 
Published: December 2008

AbstractThe effect of oxidative stress on the function of brain synapse, the difference in susceptibility of synapse to hyperoxia with age, and the changes in vitamin E status by stress and aging were investigated. Synaptic membrane permeability to sucrose was increased with age. When rats were subjected to hyperoxia, the membrane permeability on each age increased significantly. The susceptibility of synapse of 25 month old rats exposed to stress was about 2.5 times higher than unexposed old rats. The synaptic plasma membrane fluidity decreased significantly either in response to hyperoxia or during aging. The thiobarbituric acid reactive substances (TBARS) in the synaptic plasma membranes increased with age, and those in the membranes of oxygen‐exposed rats were higher than in the unexposed rats. The cholesterol/phospholipids (C/P) ratio of the membranes increased significantly with age, and the values in the membranes of oxygen‐exposed rats increased more significantly than in unexposed rats of each age. In a measurement of fatty acid content in the membranes, the content of docosahexaenoic acid (DHA, C22:6) decreased significantly during aging and by hyperoxia. These results suggest that free radicals derived from oxygen may attack nerve terminals and peroxidize the membrane, resulting in the deterioration of function of brain synapse, and that susceptibility of synapse to oxidative stress was significantly increased with age. Vitamin E content in the synaptic plasma membranes decreased with age. When rats were subjected to oxidative stress, the content was lower in each age than in normal rat membranes. An intraperitoneal administration of vitamin E prior to stress reduced these abnormalities. It is obvious that vitamin E contributes to the protection against nerve terminal dysfunction caused by oxidative stress.
Identification by differential display PCR of the selenoprotein thioredoxin reductase as a 1α,25(OH)_2‐vitamin D_3‐responsive gene in human osteoblasts — regulation by selenite
Authors: Schütze N. , Bachthaler M. , Lechner A. , Köhrle J. , Jakob F. 
Published: December 2008

Abstract1α,25(OH)2 vitamin D3 (1,25(OH)2D3) is a potent hormone, stimulating bone cell growth and differentiation. In order to detect novel targets for 1,25(OH)2D3 action, we applied differential display PCR (ddPCR) to human fetal osteoblasts (FOB cells). By ddPCR analysis, we identified the selenoprotein thioredoxin reductase (TRR) as a 1,25(OH)2D3‐responsive gene. In FOB cells, the response of TRR mRNA steady state levels to 1,25(OH)2D3 was fast and transient. Maximal stimulation was observed after one hour of 1,25(OH)2D3 treatment, thereafter TRR steady state mRNA levels declined to control levels. This transient response of TRR mRNA was not reflected at the TRR enzyme activity level upon treatment with 1,25(OH)2D3 for up to 48 h. Sodium selenite added to differentiated FOB cells increased TRR enzyme activity 2.6‐fold, whereas no selenite effect on TRR mRNA steady state levels was measurable. Our data might provide a link between the induction of a differentiation program by 1,25(OH)2D3 and the expression of the selenium responsive TRR system in human osteoblasts.
Ribonucleotide reductase in Bacillus subtilis — evidence for a Mn‐dependent enzyme
Authors: Mohamed S. F. , Gvozdiak O. R. , Stallmann D. , Griepenburg U. , Follmann H. , Auling G. 
Published: December 2008

AbstractThe reduction of 2′‐ribonucleotides to 2′‐deoxyribonucleotides, a unique step in DNA formation, is catalyzed by ribonucleotide reductase (RRase), an allosterically regulated, cell cycle‐dependent enzyme. This work reports a reversible impairment of DNA formation and ribonucleotide reduction upon manganese depletion in Bacillus subtilis demonstrated through in vivo labeling with nucleic acid precursors and enzyme assays with ether‐permeabilized cells. No deoxyadenosylcobalamin‐dependent reduction of ribonucleotides was detected in the cytosol, and the properties of a partially purified enzyme fraction, i.e., sensitivity towards EDTA and hydroxyurea (HU), indicated a metal‐dependent type of RRase. The enzyme was enriched by gel filtration on Superose ™ 12 from glycerol‐ or fumarate‐grown cells and submitted to Q‐band electron paramagnetic resonance (EPR) spectroscopy for further characterization of the metal center. A distinct Mn(II) signal was obtained in both preparations characteristic of a protein‐bound manganese in a mononuclear metal center with axial symmetry. The intensity of this Mn signal was not affected by addition of the radical scavenger HU (10 mM) but reduced in the presence of 2.5 mM EDTA. On the basis of these results, we suggest that Bacillus subtilis has a Mn‐dependent ribonucleotide reductase.
Oxidative stress, antioxidant defences and aging
Authors: Lenaz Giorgio , Cavazzoni Marika , Genova Maria Luisa , D'Aurelio Marilena , Pich Milena Merlo , Pallotti Francesco , Formiggini Gabriella , Marchetti Mario , Castelli Giovanna Parenti , Bovina Carla 
Published: December 2008

AbstractApoptosis and aging share common mechanisms in oxidative stress and mitochondrial involvement. Treatment of cultured neuroblastoma cells with a radical initiator induced apoptosis; raise in hydrogen peroxide and release of cytochrome c from mitochondria preceded collapse of mitochondrial potential and cell death. In rat hepatocytes treated with adriamycin incubation with exogenous Coenzyme Q10 counteracted the drug‐induced increase of hydrogen peroxide and the fall of the mitochondrial potential, thus demonstrating the quinone antioxidant effect.Complex I activity and its rotenone sensitivity decreased in brain cortex non‐synaptic mitochondria from old rats; a 5 kb mitochondrial DNA deletion was found only in the old rats. A similar behavior was found in human platelets from old individuals. The postulated energy decline was confirmed by the inhibitor sensitivities of platelet aggregation and lactate production. The lack of the 5 kb deletion in platelets throws doubts on mitochondrial DNA lesions as the only causes of mitochondrial dysfunction in aging.
Some new aspects of creatine kinase (CK): compartmentation, structure, function and regulation for cellular and mitochondrial bioenergetics and physiology
Authors: Wallimann Theo , Dolder Max , Schlattner Uwe , Eder Michael , Hornemann Thorsten , O'Gorman Eddie , Rück Alex , Brdiczka Dieter 
Published: December 2008

AbstractCreatine kinase (CK) isoenzymes, specifically located at places of energy demand and energy production, are linked by a phosphocreatine/creatine (PCr/Cr) circuit, found in cells with intermittently high energy demands. Cytosolic CKs, in close conjunction with Ca2+‐pumps, play a crucial role for the energetics of Ca2+‐homeostasis. Mitochondrial Mi‐CK, a cuboidal‐shaped octamer with a central channel, binds and crosslinks mitochondrial membranes and forms a functionally coupled microcompartment with porin and adenine nucleotide translocase for vectorial export of PCr into the cytosol. The CK system is regulated by AMP‐activated protein kinase via PCr/Cr and ATP/AMP ratios. Mi‐CK stabilizes and cross‐links cristae‐ or inner/outer membranes to form parallel membrane stacks and, if overexpressed due to creatine depletion or cellular energy stress, forms those crystalline intramitochondrial inclusions seen in some mitochondrial cytopathy patients. Mi‐CK is a prime target for free radical damage by peroxynitrite. Mi‐CK octamers, together with CK substrates have a marked stabilizing and protective effect against mitochondrial permeability transition pore opening, thus providing a rationale for creatine supplementation of patients with neuromuscular and neurodegenerative diseases.
Imaging the mitochondrial permeability transition pore in intact cells
Authors: Petronilli Valeria , Miotto Giovanni , Canton Marcella , Colonna Raffaele , Bernardi Paolo , Lisa Fabio Di 
Published: December 2008

AbstractThe involvement of mitochondrial permeability transition pore (MTP) in cellular processes is generally investigated by indirect means, such as changes in mitochondrial membrane potential or pharmacological inhibition. However, such effects could not be related univocally to MTP. In addition, source of errors could be represented by the increased retention of membrane potential probes induced by cyclosporin A (CsA) and the interactions between fluorescent probes.We developed a direct technique for monitoring MTP. Cells were co‐loaded with calcein‐AM and CoCl2, resulting in the quenching of the cytosolic signal without affecting the mitochondrial fluorescence. MTP inducers caused a rapid decrease in mitochondrial calcein fluorescence which, however, was not completely prevented by CsA. Besides the large and rapid efflux of calcein induced by MTP agonists, we also observed a constant and spontaneous decrease of mitochondrial calcein which was completely prevented by CsA. Thus, MTP likely fluctuates between open and closed states in intact cells.
The mitochondrial permeability transition
Authors: Bernardi Paolo , Colonna Raffaele , Costantini Paola , Eriksson Ove , Fontaine Eric , Ichas François , Massari Stefano , Nicolli Annamaria , Petronilli Valeria , Scorrano Luca 
Published: December 2008

AbstractThis review summarizes recent work on the regulation of the permeability transition pore, a cyclosporin A‐sensitive mitochondrial channel that may play a role in intracellular calcium homeostasis and in a variety of forms of cell death. The basic bioenergetics aspects of pore modulation are discussed, with some emphasis on the links between oxidative stress and pore dysregulation as a potential cause of mitochondrial dysfunction that may be relevant to cell injury.
Confocal microscopy of the mitochondrial permeability transition in necrotic cell killing, apoptosis and autophagy
Authors: Lemasters John J. , Qian Ting , Elmore Steven P. , Trost Lawrence C. , Nishimura Yoshiya , Herman Brian , Bradham Cynthia A. , Brenner David A. , Nieminen Anna‐Liisa 
Published: December 2008

AbstractOnset of the cyclosporin‐A‐sensitive mitochondrial permeability transition (MPT) in individual mitochondria within living cells can be visualized by laser scanning confocal microscopy. The MPT is a causative event in many types of necrotic and apoptotic cell death, including oxidative stress, ischemia/reperfusion injury, Ca2+ionophore toxicity and tumor necrosis factor alpha (TNFα) induced apoptosis, and may contribute to Reye's‐related drug toxicity. Pyridine nucleotide oxidation, mitochondrial generation of reactive oxygen species, and increased mitochondrial Ca2+and pH can each promote onset of the MPT in situ. The MPT can also be directly visualized during TNFα‐induced apoptosis to hepatocytes. Mitochondria spontaneously depolarize in situ after nutrient deprivation before entering an acidic lysosomal compartment, suggesting that the MPT precedes the normal process of mitochondrial autophagy. We propose a model in which onset of the MPT to increasing numbers of mitochondria leads progressively to autophagy, apoptosis and necrotic cell death.