bluuebunny/crossref_metadata_2025_split huggingface dataset:
Kinetic control of internal electron transfer in cytochrome c oxidase
Authors: Brunori Maurizio , Giuffré Alessandro , D'Itri Emilio , Sarti Paolo 
Published: December 2008

AbstractTwo alternative hypotheses have been proposed to account for the relatively slow (ms) internal eT observed in the oxidized cyt c oxidase. The thermodynamic control hypothesis states that eT between cyt a and a3 is very fast (μs), but the apparent reduction of cyt a3 is slow because thermodynamics favors reduced cyt a. Whereas the kinetic control hypothesis states that inter‐heme eT is intrinsically slow (ms), for the oxidized binuclear center.Monitoring by stopped flow the anaerobic reduction of the oxidized enzyme by ruthenium hexamine in the absence and presence of CO or NO, used as “trapping” ligands for cyt a32+, we found that the rate of formation of the cyt a32+—NO adduct (k′ ≈︁ 20–25 s−1) is independent of the concentration of ruthenium hexamine and NO. We conclude that in the oxidized enzyme the two hemes are not in very rapid redox equilibrium and internal eT is kinetically controlled.
The structure and function of the brown fat uncoupling protein UCP1: current status
Authors: Rial Eduardo , González‐Barroso M. Mar , Fleury Christophe , Bouillaud Frédéric 
Published: December 2008

AbstractThe uncoupling protein of brown adipose tissue (UCP1) is a transporter that allows the dissipation as heat of the proton gradient generated by the respiratory chain. The discovery of new UCPs in other mammalian tissues and even in plants suggests that the proton permeability of the mitochondrial inner membrane can be regulated and its control is exerted by specialised proteins. The UCP1 is regulated both at the gene and the mitochondrial level to ensure a high thermogenic capacity to the tissue. The members of the mitochondrial transporter family, which includes the UCPs, present two behaviours with carrier and channel transport modes. It has been proposed that this property reflects a functional organization in two domains: a channel and a gating domain. Mounting evidence suggest that the matrix loops contribute to the formation of the gating domain and thus they are determinants to the control of transport activity.
Protein translocation into mitochondria
Authors: Káldi Krisztina , Neupert Walter 
Published: December 2008

AbstractThe mitochondrial membranes contain translocation machineries (&&num;147;preprotein translocases&&num;148;) which facilitate transport of proteins from the cytosol into the mitochondria. The TOM complex is localized in the outer membrane. Two translocases have been characterized in the inner membrane: the Tim23‐Tim17 complex and the Tim22 complex which differ in their specificities for preproteins. The TOM and TIM complexes can act in a coordinated fashion to facilitate the insertion of preproteins into the mitochondrial membranes as well as the translocation into the internal compartments, the intermembrane space and the matrix. We discuss insights into the function of components of the translocases, illustrated by examples for mechanisms of protein sorting into the different compartments of mitochondria.
Electron microscopic tomography of rat‐liver mitochondria and their interactions with the endoplasmic reticulum
Authors: Mannella Carmen A. , Buttle Karolyn , Rath Bimal K. , Marko M. 
Published: December 2008

AbstractElectron microscopic tomography can provide a complete three‐dimensional range of information about subcellular structures. Applied to mitochondria, it has shown that the conventional textbook model of this organelle is incorrect. The infoldings of the inner membrane (called cristae) are connected by narrow tubular regions to each other and to the outside, suggesting that internal diffusion of ions, metabolites and proteins may be restricted. Tomographic reconstruction of mitochondria in situ indicates these organelles may occur in clusters with stacks of endoplasmic reticulum, forming extended structures that may be involved in [Ca++] regulation.
Role of mitochondria in metabolism‐secretion coupling of insulin release in the pancreatic β‐cell
Authors: Maechler Pierre , Wollheim Claes B. 
Published: December 2008

AbstractThe control of insulin secretion from the pancreatic β‐cell involves a complex cascade of events in which the mitochondria play a central role. In the consensus model this role is essentially restricted to the production of ATP promoting membrane depolarisation and a rise in cytosolic [Ca2+]. Evidence for the generation of an additional mitochondrial factor implicated in metabolism‐secretion coupling is provided in this review. Although not yet identified, the formation of this putative factor requires an increase of [Ca2+] in the mitochondrial matrix together with a supply of carbons to the tricarboxylic acid (TCA) cycle. In this model, calcium activates matrix dehydrogenases, in particular those of the TCA cycle. This enables the synthesis of the mitochondrial factor from the TCA cycle intermediates. Experimental evidence gathered in permeabilised cells largely supports this model.
Apolipoprotein E (ApoE), a Bmp‐2 (bone morphogenetic protein) upregulated gene in mesenchymal progenitors (C3H10T1/2), is highly expressed in murine embryonic development
Authors: Bächner Dietmar , Schröder Dietmar , Betat Nicole , Ahrens Marion , Gross Gerhard 
Published: December 2008

AbstractApolipoprotein E (ApoE) was identified as upregulated by Bmp‐2 (bone morphogenetic protein‐2) in the murine mesenchymal progenitor cell line C3H10T1/2 by a subtractive cloning strategy. Expression of recombinant Bmps in mesenchymal C3H10T1/2 progenitors results in the differentiation into the osteogenic, the chondrogenic, and the adipogenic lineage. In addition, ApoE is also expressed in primary osteoblasts isolated from murine calvariae late in the in vitro osteoblast developmental sequence. To infer possible roles of ApoE in organogenesis and tissue differentiation, ApoE expression during mouse embryonic development was analyzed in murine midgestation and late embryonic development by in situ hybridization. ApoE is highly expressed at many sites of organ development (liver, brain, heart, eye, lung), probably in a subset of neural crest cells and ectodermal derivatives suggestive for important functions of ApoE during embryonic differentiation and organ development.
Localization and mobility of coenzyme Q in lipid bilayers and membranes
Authors: Lenaz Giorgio , Fato Romana , Di Bernardo Salvatore , Jarreta Diana , Costa Angela , Genova Maria Luisa , Castelli Giovanna Parenti 
Published: December 2008

AbstractWe have studied the mobility of coenzyme Q (CoQ) in lipid bilayers and mitochondrial membranes in relation to the control of electron transfer activities. A molecular dynamics computer simulation in the vacuum yielded a folded structure for CoQ10, with a length of only 21 Å. Using this information we were able to calculate diffusion coefficients in the range of 10−6 cm2/s in good agreement with those found experimentally by fluorescence quenching of pyrene derivatives. To investigate if CoQ diffusion may represent the rate‐limiting step of electron transfer, we reconstituted complexes I and III and assayed the resulting NADH‐cytochrome c reductase activity in presence of different CoQ10 levels and at different distances between complexes; the experimental turnovers were higher than the collision frequencies calculated using diffusion coefficients of 10−9 cm2/s but compatible with values found by us by fluorescence quenching. Since the experimental turnovers are independent of the distance between complexes, we conclude that CoQ diffusion is not rate‐limiting for electron transfer.
Proton translocation in the respiratory chain involving ubiquinone — a hypothetical semiquinone switch mechanism for complex I
Authors: Brandt Ulrich 
Published: December 2008

AbstractThe protonmotive Q‐cycle is the generally accepted reaction scheme of the cytochrome bc1 complex of the respiratory chain. It employs the redox‐dependent protonation and deprotonation of ubiquinone (coenzyme Q10) to translocate protons accross the inner mitochondrial or bacterial plasma membrane. The requirements for the operation of a similar mechanism in proton translocating NADH:ubiquinone oxidoreductase (complex I) and the specific roles of the ‘Rieske’ iron‐sulfur center in the cytochrome bc1 complex and iron‐sulfur center N‐2 in complex I are discussed.Recent results suggest that there is only one ubiquinone‐reactive site in complex I which seems to exclude a classical Q‐cycle type mechanism. Therefore, a “semiquinone switch” mechanism is proposed involving one tightly bound and one substrate quinone. It is based on the same principles as a Q‐cycle, but is a localized rather than a ligand conduction type mechanism.
Metabolism of coenzyme Q10: Biliary and urinary excretion study in guinea pigs
Authors: Nakamura T. , Ohno T. , Hamamura K. , Sato T. 
Published: December 2008

AbstractBiliary and urinary metabolites were examined after intravenous administration of 14C‐coenzyme Q10 (14C‐CoQ) to guinea pigs. Cumulative recovery of administered radioactivity for up to 8 hours by bile drainage was 4.8%. The greater part of radioactivity was detected in conjugate form. After hydrolyzing with β‐glucuronidase, aglycone fragments were subjected to methylation and reductive acetylation. The main metabolite was demonstrated to be Q acid‐I 1,4‐hydroquinone diacetate methyl ester (M‐1) on HPLC. Then, the main metabolite was assumed to be glucuronide of 2,3‐dimethoxy‐5‐methyl‐6‐(3′‐methyl‐5′‐carboxy‐2′‐pentenyl)‐1,4‐benzohydroquinone [Q acid‐I hydroquinone]. The cumulative urinary recovery of the administered radioactivity over 48 hours was 8.3%. The labeled samples were treated similarly to bile. The urinary metabolites of CoQ10 consisted of unconjugated and conjugated forms. Lyophilized urine was treated as a bile sample and analyzed. The two major metabolites were assigned to be M‐1 and Q acid‐II 1,4‐hydroquinone diacetate methyl ester (M‐2). Then, the two metabolites were assumed to be composed of Q acid‐I and 2,3‐dimethoxy‐5‐methyl‐6‐(3′‐carboxypropyl)‐1,4‐benzoquinone (Q acid‐II) in free and corresponding hydroquinone conjugate forms. To investigate the effect of exogenous labeled CoQ10 on unlabeled CoQ10 (endogenous) metabolites in urine, simultaneous quantitative determination was performed using deuterium labeled CoQ10 (CoQ10‐d5). Urine collected over a 72‐hour period after intravenous administration of CoQ10‐d5 was processed similarly to that described above and two derivatized metabolites (M‐1 and M‐2) were quantified by gas chromatography‐mass fragmentography with the multi‐ion detection method. The analytical results showed that the addition of exogenous labeled CoQ10 did not influence the metabolism (or breakdown) of unlabeled (endogenous) CoQ10.
Induction of endogenous coenzyme Q biosynthesis by administration of peroxisomal inducers
Authors: Turunen Mikael , Sindelar Pavel , Dallner Gustav 
Published: December 2008

AbstractA large number of chemical compounds have been identified which cause peroxisomal proliferation and induce a number of enzymes, mainly those participating in lipid metabolism. Administration of these drugs/chemicals to rats increased coenzyme Q levels in the blood and most of the organs. Levels were raised in all cellular membranes of such organs. The extent of induction of this lipid was 8‐fold in young animals but decreased during aging and was absent at 1.5 year of age. One of the regulating factors of the mevalonate pathway is farnesol, which is produced by dephosphorylation of farnesyl‐PP and eliminated by phosphorylation including two kinases. Future research will involve a search for modified intermediary metabolites, which increase coenzyme Q synthesis and thereby efficiently elevate the level of this lipid in conditions of deficiency.
Critical aspects of the antioxidant function of coenzyme Q in biomembranes
Authors: Nohl Hans , Gille Lars , Kozlov Andrey V. 
Published: December 2008

AbstractCoenzyme Q (ubiquinone, UQ) is increasingly considered as a significant natural antioxidant, which protects biomembranes in concert withα‐tocopherol. In vitro experiments demonstrated that reduced UQ (ubiquinol) can improve the chain‐breaking activities ofα‐tocopherol by recycling the antioxidant‐derived reaction product, the chromanoxyl radical, to the native antioxidant. Less attention, however, was devoted to the antioxidant‐derived reaction products of reduced UQ. Although bothα‐tocopherol and ubiquinol were found to be equally effective in scavenging chain‐propagating lipid radicals,α‐tocopherol protected lipid membranes from lipid peroxidation more efficiently than ubiquinol. The present study not only provides data which document this discrepancy but also contributes experimental data on the existence of ubiquinol derived pro‐oxidants, which give an explanation of this phenomenon.
A possible role of coenzyme Q10 in the etiology and treatment of Parkinson's disease
Authors: Shults Clifford W. , Haas Richard H. , Beal M. Flint 
Published: December 2008

AbstractParkinson's disease (PD) is a degenerative neurological disorder. Recent studies have demonstrated reduced activity of complex I of the electron transport chain in brain and platelets from patients with PD. Platelet mitochondria from parkinsonian patients were found to have lower levels of coenzyme Q10 (CoQ10) than mitochondria from age/sex‐matched controls. There was a strong correlation between the levels of CoQ10 and the activities of complexes I and II/III. Oral CoQ10 was found to protect the nigrostriatal dopaminergic system in one‐year‐old mice treated with MPTP, a toxin injurious to the nigrostriatal dopaminergic system. We further found that oral CoQ10 was well absorbed in parkinsonian patients and caused a trend toward increased complex I activity. These data suggest that CoQ10 may play a role in cellular dysfunction found in PD and may be a potential protective agent for parkinsonian patients.
Overview of the use of CoQ10 in cardiovascular disease
Authors: Langsjoen Peter H. , Langsjoen Alena M. 
Published: December 2008

AbstractThe clinical experience in cardiology with CoQ10 includes studies on congestive heart failure, ischemic heart disease, hypertensive heart disease, diastolic dysfunction of the left ventricle, and reperfusion injury as it relates to coronary artery bypass graft surgery. The CoQ10‐lowering effect of HMG‐CoA reductase inhibitors and the potential adverse consequences are of growing concern. Supplemental CoQ10 alters the natural history of cardiovascular illnesses and has the potential for prevention of cardiovascular disease through the inhibition of LDL cholesterol oxidation and by the maintenance of optimal cellular and mitochondrial function throughout the ravages of time and internal and external stresses. The attainment of higher blood levels of CoQ10 (>3.5 μg/ml) with the use of higher doses of CoQ10 appears to enhance both the magnitude and rate of clinical improvement. In this communication, 34 controlled trials and several open‐label and long‐term studies on the clinical effects of CoQ10 in cardiovascular diseases are reviewed.
Coenzyme Q10 treatment in serious heart failure
Authors: Munkholm H. , Hansen H. H. T. , Rasmussen K. 
Published: December 2008

AbstractSeveral noninvasive studies have shown the effect on heart failure of treatment with coenzyme Q10. In order to confirm this by invasive methods we studied 22 patients with mean left ventricular (LV) ejection fraction 26%, mean LV internal diameter 71 mm and in NYHA class 2‐3. The patients recieved coenzyme Q10 100 mg twice daily or placebo for 12 weeks in a randomized double‐blinded placebo controlled investigation.Before and after the treatment period, a right heart catheterisation was done including a 3 minute exercise test.The stroke index at rest and work improved significantly, the pulmonary artery pressure at rest and work decreased (significantly at rest), and the pulmonary capillary wedge pressure at rest and work decreased (significantly at 1 min work).These results suggest improvement in LV performance. Patients with congestive heart failure may thus benefit from adjunctive treatment with coenzyme Q10.
Coenzyme Q10improves the tolerance of the senescent myocardium to aerobic and ischemic stress: Studies in rats and in human atrial tissue
Authors: Rosenfeldt Franklin L. , Pepe Salvatore , Ou Ruchong , Mariani Justin A. , Rowland Michael A. , Nagley Phillip , Linnane Anthony W. 
Published: December 2008

AbstractThe inferior recovery of cardiac function after interventional cardiac procedures in elderly patients compared to younger patients suggests that the aged myocardium is more sensitive to stress. We report two studies that demonstrate an age‐related deficit in myocardial performance after aerobic and ischemic stress and the capacity of CoQ10treatment to correct age‐specific diminished recovery of function. In Study 1 the functional recovery of young (4 mo) and senescent (35 mo) isolated working rat hearts after aerobic stress produced by rapid electrical pacing was examined. After pacing, the senescent hearts, compared to young, showed reduced recovery of pre‐stress work performance. CoQ10pretreatment (daily intraperitoneal injections of 4 mg/kg CoQ10for 6 weeks) in senescent hearts improved their recovery to match that of young hearts. Study 2 tested whether the capacity of human atrial trabeculae (obtained during surgery) to recover contractile function, following ischemic stressIn vitro(60 min), is decreased with age and whether this decrease can be reversed by CoQ10. Trabeculae from older individuals (≥ 70 yr) showed reduced recovery of developed force after simulated ischemia compared to younger counterparts (<70 yr). Notably, this age‐associated effect was prevented in trabeculae pretreatedIn vitro(30 min at 24°C) with CoQ10(400 μM). We measured significantly lower CoQ10content in trabeculae from ≥ 70 yr patients.In vitropretreatment raised trabecular CoQ10content to similar levels in all groups. We conclude that, compared to younger counterparts, the senescent myocardium of rats and humans has a reduced capacity to tolerate ischemic or aerobic stress and recover pre‐stress contractile performance, however, this reduction is attenuated by CoQ10pretreatment.
Bioenergetic effect of liposomal coenzyme Q10 on myocardial ischemia reperfusion injury
Authors: Niibori Koki , Wroblewski Krzystof P. , Yokoyama Hitoshi , Crestanello Juan A. , Whitman Glenn J. R. 
Published: December 2008

AbstractThe antioxidant and bioenergetic effects of CoQ10 are well known but its clinical utility is limited by the requirement for enteral administration. A newly developed liposomal CoQ10 (CoQ) is water soluble and capable of intravenous administration.The purpose of this study is to determine the mechanism by which acute administration CoQ protects myocardium from reperfusion (Rp) injury. Rats were pretreated with CoQ 10 mg/kg i.v. 30 min prior to the experiment. Control rats were pretreated with liposome only. Hearts were excised and subjected to equilibration, 25 min of normothermic ischemia and 40 min of Rp on a Langendorff apparatus. At end Rp, CoQ hearts recovered 74 ± 5% of their DP vs. 50 ± 9% in control (p<0.05). Aerobic efficiency was maintained (0.66 ± 0.02 vs. control, 0.5 ± 0.04, p<0.003) and CoQ hearts lost less CK activity vs. control (p<0.02). PCr and ATP were higher than control (p<0.05, 0.02, respectively). Results show that i.v. CoQ improves recovery of function, aerobic efficiency, CK activity, and recovery of PCr and ATP after Rp. This suggests that acute administration of liposomal CoQ improves myocardial tolerance to I/R via its role as an antioxidant as well as improving oxygen utilization and high energy phosphate production.
High serum coenzyme Q10, positively correlated with age, selenium and cholesterol, in Inuit of Greenland. A pilot study
Authors: Pedersen H. S. , Mortensen S. A. , Rohde M. , Deguchi Y. , Mulvad G. , Bjerregaard P. , Hansen J. C. 
Published: December 2008

AbstractGreenlanders (Eskimos) have low prevalence of ischaemic heart disease, partly explained by a lower extent of atherosclerosis and a low n‐6/n‐3 ratio of polyunsaturated fatty acids. As atherosclerosis is also a result of oxidative stress, the total antioxidative readiness could have a substantial impact. From a health survey we chose the subpopulation from the most remote area, where the traditional Greenlandic diet with high intake of sea mammals and fish predominates. The mean (SD) of S‐CoQ10 in males was 1.495 (0.529) nmol/ml and 1.421 (0.629) nmol/ml in females, significantly higher (p<0.001) compared to a Danish population. In a linear multiple regression model the S‐CoQ10 level is significantly positively associated with age and S‐selenium in males, and S‐total cholesterol in females. The high level of CoQ10 in Greenlanders probably reflects diet, since no bioaccumulation takes place, and it could probably be a substantial part of the antioxidative defense.
Olive oil supplemented with vitamin E affects mitochondrial coenzyme Q levels in liver of rats after an oxidative stress induced by adriamycin
Authors: Quiles J. L. , Ramirez‐Tortosa M. C. , Huertas J. R. , Ibañez S. , Gomez J. A. , Battino M. , Mataix J. 
Published: December 2008

AbstractIn this study we have evaluated the supplementation of olive oil with vitamin E on coenzyme Q concentration and lipid peroxidation in rat liver mitochondrial membranes. Four groups of rats were fed on virgin olive, olive, olive plus 200 mg/kg of vitamin E or sunflower oils as lipid dietary source. To provoke an oxidative stress rats were administered intraperitoneally 10 mg/kg/day of adriamycin the last two days of the experiment. Animals fed on olive oil plus vitamin E had significantly higher coenzyme Q and vitamin E levels but a lower mitochondrial hydroperoxide concentration than rats fed on olive oil. Retinol levels were not affected, by either different diets or adriamycin treatment. In conclusion, an increase in coenzyme Q andα‐tocopherol in these membranes can be a basis for protection against oxidation and improvement in antioxidant capacity.
Protective effect of exogenous coenzyme Q in rats subjected to partial hepatic ischemia and reperfusion
Authors: Genova Maria Luisa , Bonacorsi Elisa , D'Aurelio Marilena , Formiggini Gabriella , Nardo Bruno , Cuccomarino Salvatore , Turi Paola , Pich Milena Merlo , Lenaz Giorgio , Bovina Carla 
Published: December 2008

AbstractIn a surgical model of liver ischemia lipid peroxidation occurs, as shown by increase of lipid peroxidation end products, endogenous CoQ9 is oxidized and mitochondrial respiration is lowered; however, pre‐treatment of the rats by i.p. injection of CoQ10 for 14 days normalizes the above parameters, presumably by way of the observed high extent of reduction of the incorporated quinone; moreover, liver homogenates of the CoQ10‐treated rats are more resistant than those of non‐treated rats to oxidative stress induced by an azido free radical initiator. This preliminary study suggests that CoQ10 pre‐treatment can be of beneficial effect against oxidative damage during liver surgery transplantation.