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1.
Acetyl-L-carnitine treatment stimulates oxygen consumption and biosynthetic function in perfused liver of young and old rats 总被引:1,自引:0,他引:1
Mollica MP Iossa S Soboll S Liverini G 《Cellular and molecular life sciences : CMLS》2001,58(3):477-484
The effect of treatment with acetyl-L-carnitine on hepatic mitochondrial respiration and biosynthetic function in perfused
liver from young (90 days) and old (22-24 months) rats was studied. Rats were given a 1.5% (w/v) solution of acetyl-L-carnitine
in their drinking water for 1 month and oxygen consumption together with the rate of gluconeogenesis, urea synthesis, and
ketogenesis with and without added substrates were measured in perfused liver. Mitochondrial oxygen consumption was also assessed
in liver homogenate and isolated mitochondria to determine the maximal capacity for oxidative phosphorylation. Acetyl-L-carnitine
treatment almost completely restored the age-dependent decline in oxygen consumption, gluconeogenesis, urea synthesis, and
ketogenesis found in perfused liver of old rats to the levels found in young rats. In addition, acetyl-L-carnitine treatment
increased oxygen consumption and biosynthetic function in perfused liver from young rats. After acetyl-L-carnitine treatment,
we found detectable 3-oxoacyl-CoA-transferase activity associated with a consumption of ketone bodies in young and old rats.
Finally, oxygen consumption measured in homogenate and isolated mitochondria did not change with age and acetyl-L-carnitine
treatment. Our results show that in perfused liver, acetyl-L-carnitine treatment slows the age-associated decline in mitochondrial
respiration and biosynthetic function. In addition, treatment of young rats with acetyl-L-carnitine has a stimulating effect
on liver metabolism, probably through an increase in ATP production.
Received 25 October 2000; received after revision 14 December 2000; accepted 11 January 2001 相似文献
2.
Mitochondrial respiratory function and antioxidant capacity in normal and cirrhotic livers following partial hepatectomy 总被引:11,自引:0,他引:11
For many liver malignancies, major hepatectomy is the usual therapy. Although a normal liver has a tremendous capacity for regeneration, liver hepatectomy in humans is usually carried out on a diseased liver and, in such cases, liver regeneration takes place in a cirrhotic remnant. Mitochondrial function in cirrhotic livers shows a variety of changes compared to control livers. This study investigated how mitochondrial respiratory function and antioxidant capacity change following partial hepatectomy of cirrhotic livers, because liver regeneration requires greater energy demands and control of oxidative stress. Cirrhosis was induced in male Wistar-Furth rats by administration of thioacetamide. NADH-cytochrome c reductase activity, mitochondrial glutathione peroxidase activity and mitochondrial GSH levels were all significantly lowered in cirrhotic livers and in the cirrhotic remnants up to 72 h after 70% hepatectomy when compared to the corresponding controls. Lower respiratory control ratios with succinate as substrate were also observed from 6 to 48 h post-hepatectomy. At 24 h post-hepatectomy, higher levels of lipid peroxidation were observed. We conclude that, compared to the controls, cirrhotic livers have diminished oxidative phosphorylation capabilities due to changes in NADH and FADH2-linked respiration as well as impaired antioxidant defenses following partial hepatectomy. Both of these factors, if critical, could then impede liver regeneration.Received 15 September 2003; received after revision 26 October 2003; accepted 19 November 2003 相似文献
3.
Patrushev M Kasymov V Patrusheva V Ushakova T Gogvadze V Gaziev A 《Cellular and molecular life sciences : CMLS》2004,61(24):3100-3103
Fragments of mitochondrial DNA are released from mitochondria upon opening of the mitochondrial permeability transition pore. Cyclosporin A, an inhibitor of pore opening, completely prevented the release of mitochondrial fragments. Induction of mitochondrial permeability transition and subsequent release of the fragments of mitochondrial DNA could be one cause of genomic instability in the cell.Received 22 September 2004; received after revision 11 October 2004; accepted 18 October 2004M. Patrushev, V. Kasymov and V. Patrusheva contributed equally to this work. 相似文献
4.
Lionetti L Crescenzo R Mollica MP Tasso R Barletta A Liverini G Iossa S 《Cellular and molecular life sciences : CMLS》2004,61(11):1366-1371
This study was designed to examine the effect of youth-adulthood transition on hepatic mitochondrial energy efficiency. The changes in basal and palmitate-induced proton leak, which contribute to mitochondrial efficiency, were evaluated in mitochondria isolated from the liver of young and adult rats. Alterations in mitochondrial cytochrome oxidase and aconitase specific activities, and in adenine nucleotide translocator content were also assessed. There was no difference in basal proton leak or thermodynamic coupling and efficiency of oxidative phosphorylation in liver mitochondria between the two rat groups. On the other hand, palmitate-induced proton leak increased significantly in adult rats. The function of this uncoupling could be avoidance of elevated formation of reactive oxygen species, which are known to accelerate ageing.Received 17 February 2004; received after revision 30 March 2004; accepted 1 April 2004 相似文献
5.
Justo R Alcolea MP Colom B Riera AN Gianotti M García-Palmer FJ 《Cellular and molecular life sciences : CMLS》2002,59(12):2199-2209
To establish the role of mitochondrial subpopulations in the mitochondrial maturation process, we studied morphological and
functional changes in the mitochondria of different mammalian conceptus tissues during the organogenic and the placentation
processes. Mitochondrial subpopulations of three different conceptus tissues, embryo and visceral yolk sac placenta on gestational
days 11, 12 and 13 and placenta on days 12 and 13, were examined morphologically by transmission electron microscopy. Cytochrome
oxidase activity and protein levels were also measured in each mitochondrial subpopulation. The results indicate two different
mitochondrial subpopulation profiles: a homogeneous one, which corresponds to immature mitochondria, and a heterogeneous one,
which represents the mature mitochondria. The three tissues studied show different morphologic and metabolic patterns of mitochondrial
maturation during the placentation process, rendering them suitable as experimental models to establish the p
ossible relationship between mitochondrial maturation and the mitochondrial subpopulations.
Received 5 August 2002; received after revision 23 September 2002; accepted 8 October 2002
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ID="*"Corresponding author. 相似文献
6.
A population of ventral neural tube cells has recently been shown to migrate out of the hind brain neural tube via the vagus
nerve and contribute to the developing gastrointestinal tract. Since liver is also innervated by the vagus nerve, we sought
to determine if these cells also migrate into the liver. Ventral neural tube cells in the caudal hindbrain of chick embryos
were tagged with a replication-deficient retroviral vector containing the LacZ gene on embryonic day 2. Embryos were processed
for detection of labeled cells on embryonic day 5 and 11. Labeled cells were seen in the liver on both days and identified
as hepatocytes. Previously, it was believed that all hepatocytes develop from the gut endoderm. Results of the present study
show an additional source for the formation of liver cells.
Received 25 August 1998; received after revision 5 November 1998; accepted 5 November 1998 相似文献
7.
Visual pigment: G-protein-coupled receptor for light signals 总被引:5,自引:0,他引:5
The visual pigment present in photoreceptor cells is a prototypical G-protein-coupled receptor (GPCR) that receives a light
signal from the outer environment using a light-absorbing chromophore, 11-cis-retinal. Through cis-trans isomerization of the chromophore, light energy is transduced into chemical free energy, which
is in turn utilized for conformational changes in the protein to activate the retinal G-protein. In combination with site-directed
mutagenesis, various spectroscopic and biochemical studies identified functional residues responsible for chromophore binding,
color regulation, intramolecular signal transduction and G-protein coupling. Extensive studies reveal that these residues
are localized into specific domains of visual pigments, suggesting a highly manipulated molecular architecture in visual pigments.
In addition to the recent findings on dysfunctional mutations in patients with retinitis pigmentosa or congenital night blindness,
the mechanism of intramolecular signal transduction in visual pigments and their evolutionary relationship are discussed.
Received 20 July 1998; received after revision 9 September 1998; accepted 23 September 1998 相似文献
8.
The structure and function of heterotrimeric G protein subunits is known in considerable detail. Upon stimulation of a heptahelical
receptor by the appropriate agonists, the cognate G proteins undergo a cycle of activation and deactivation; the α-subunits and the βγ-dimers interact sequentially with several reaction partners (receptor, guanine nucleotides and effectors as well as regulatory
proteins) by exposing appropriate binding sites. For most of these domains, low molecular weight ligands have been identified
that either activate or inhibit signal transduction. These ligands include short peptides derived from receptors, G protein
subunits and effectors, mastoparan and related insect venoms, modified guanine nucleotides, suramin analogues and amphiphilic
cations. Because compounds that act on G proteins may be endowed with new forms of selectivity, we propose that G protein
subunits may therefore be considered as potential drug targets.
Received 18 September 1998; received after revision 6 November 1998; accepted 11 November 1998 相似文献
9.
Summary Similar diurnal periodicity in oxygen consumption of liver slices in Wistar rats was observed as that previously found in Sprague-Dawley rats. The rate of oxygen consumption was low in the morning and high in the evening. After inversion of lighting regimes, the phase shifted and reached the reversal curve in about 30 days. On the basis of these findings, it is estimated that diurnal periodicity in oxygen consumption of liver slices is influenced by alteration of the periods of light and darkness. Liver glycogen rhythm showed a reversed correlation to that of oxygen consumption in both lighting regimes. 相似文献
10.
Analysis of nuclear apoptotic process in a cell-free system 总被引:2,自引:0,他引:2
We report an analysis of the apoptotic process of mouse liver nuclei induced in a cell-free carrot cytosol system by cytochrome
c. Typical characteristics of apoptosis were observed, such as chromatin condensation, margination, apoptotic bodies and DNA
ladders. Furthermore, transmission and scanning electron microscope analysis of the apoptotic nuclei detected chromatin-free
nuclear vesicles before apoptotic bodies appeared at a comparatively late phase. When AC-YVAD-CHO, an inhibitor of caspase
6, was introduced into the system, these vesicles and apoptotic bodies disappeared completely within our study sections. We
confirmed the results using whole-mount electron microscopy, and found that although the nuclear lamina was destroyed early,
the nuclear matrix largely remained intact during the course of apoptosis. The nuclear matrix played an important role in
maintaining the integrity of apoptotic cells and connecting the apoptotic bodies and apoptotic nucleus.
Received 29 September 2000; revised 10 December 2000; accepted 13 December 2000 相似文献
11.
Allometry of mammalian cellular oxygen consumption 总被引:3,自引:0,他引:3
R.K. Porter 《Cellular and molecular life sciences : CMLS》2001,58(5-6):815-822
In the 1930s, Max Kleiber and Samuel Brody established that the interspecies correlation between mammalian body mass and
metabolic rate (αM0.75) cannot be explained (solely) by whole body surface area (αM0.66) to volume ratios. Metabolic considerations must also be taken into account. Decreases in the proportion of visceral organ
mass to whole body mass can account for some of the whole body metabolic differences. However, superimposed upon these anatomical
differences, the metabolism of tissues and cells has been demonstrated to decrease with increasing body mass. These decreases
in oxygen consumption rates (with increasing body mass) in cells and tissues can be explained by a decrease in ATP turnover
and mitochondrial density and an increase in mitochondrial functional efficiency (decrease in proton leak). The majority of
the proton leak differences reflect differences in mitochondrial inner membrane surface area. Indeed, liver metabolism correlates
directly with liver mitochondrial inner membrane surface area. Apart from being a significant contributor (~25 %) to basal
metabolism, mitochondrial proton leak is a major factor determining the differences in basal metabolism between mammals of
different body mass.
Received 31 May 2000; received after revision 2 October 2000; accepted 14 November 2000 相似文献
12.
Structure, function and metabolism of sialic acids 总被引:9,自引:0,他引:9
Sialic acids represent a family of sugar molecules with an unusual and highly variable chemical structure that are found
mostly in the terminal position of oligosaccharide chains on the surface of cells and molecules. These special features enable
them to fulfil several important and even diametrical biological functions. Because of the great importance of sialic acids,
it is also worth having a look at their metabolism in order to get an idea of the intimate connection between structure and
function of these fascinating molecules and the often serious consequences that result from disturbances in the balance of
metabolic reactions. The latter can be due to genetic disorders that result in the absence of certain enzyme activity, leading
to severe illness or even to death.
Received 17 July 1998; received after revision 2 September 1998; accepted 2 September 1998 相似文献
13.
E. Schreider 《Cellular and molecular life sciences : CMLS》1956,12(8):315-316
Summary Ketone levels in the rat's organs (liver, muscle, lung, kidney, brain) do not seem to be correlated with the ketone level in the blood plasma. On the other hand, there are significant and high correlations between the ketone levels of different organs. These findings are not inconsistent with the generally accepted theory according to which blood distributes hepatic ketone bodies to the periphery. But ketone levels of the organs seem to be regulated not by variations of the plasma ketones, but by another common factor. At present, it is impossible to say how this regulation is effected. 相似文献
14.
Thyroid hormone controls carnitine status through modifications of γ-butyrobetaine hydroxylase activity and gene expression 总被引:1,自引:0,他引:1
Galland S Georges B Le Borgne F Conductier G Dias JV Demarquoy J 《Cellular and molecular life sciences : CMLS》2002,59(3):540-545
The carnitine system plays a key role in β-oxidation of long-chain fatty acids by permitting their transport into the mitochondrial
matrix. The effects of hypothyroidism and hyperthyroidism were studied on γ-butyrobetaine hydroxylase (BBH), the enzyme responsible
for carnitine biosynthesis in the rat. In rat liver, BBH activity was decreased in the hypothyroid state and increased in
hyperthyroid animals. The modifications in BBH activity correlated with changes in the enzyme Vmax values. These changes were
shown to be related to hepatic BBH mRNA abundance. Thyroid hormones are known to interact with lipid metabolism, in particular
by increasing long-chain fatty acid oxidation through activation of carnitine-dependent fatty acid import into mitochondria.
Our study showed that thyroid hormones also increased carnitine bioavailability.
Received 23 October 2001; received after revision 11 January 2002; accepted 15 January 2002 相似文献
15.
Alteration of mitochondrial bioenergetics due to intravenous injection of a perfluorocarbon emulsion
D. Branca S. M. Chiarelli E. Vincenti C. Tortorella G. Scutari 《Cellular and molecular life sciences : CMLS》1994,50(7):660-663
Wistar albino rats were intravenously injected with 1 ml of an oxyphoretic emulsion of perfluorobutylfurane and killed 3, 7 or 30 days later. Mitochondria isolated from the liver and kidneys of treated rats showed a small decrease in the transmembrane electrical potential and a substantial depression of the rates of both ATP synthesis and ADP-stimulated respiration. These alterations in mitochondrial oxidative phosphorylation appear to be induced by perfluorocarbon and/or tensioactive molecules interacting with hydrophobic cell structures. 相似文献
16.
Die DNS-Synthese in Leber und Niere junger Ratten. Autoradiographische Untersuchungen mit3H-Thymidin
Summary Autoradiographic studies following a single i.p. injection of3H-thymidine were performed in liver and kidney parenchyma of new-born and young adult rats at different ages (1, 2, 4, 7, 12, 18, 24, 30, 60 and 120 days). In 1-day-old animals the tritium index (i.e. percentage of DNA synthesizing nuclei) of both organs is lower than in the rat embryo. From 1–4 days fluctuations occur, then the tritium index rises at 7 and 12 days. But now an exponential decrease is observed up to day 120. This depression and fluctuation of the tritium index probably depends on a postpartal functional transposition and especially in the liver on a structural transformation. The mean grain density in the labelled nuclei increases from 1 up to 24 days, which is likely connected with a very high amount of endogenous thymidine in new-born rats. From day 24 the mean grain density can be taken as a relative measure for the rate of DNA synthesis. The reduction in the rate of DNA synthesis from 24–120 days is explained as a consequence of the commutation from the rapid to the slow mode in cellular proliferation.
Mit Unterstützung der Deutschen Forschungsgemeinschaft. 相似文献
Mit Unterstützung der Deutschen Forschungsgemeinschaft. 相似文献
17.
Summary Differential scanning calorimetry was employed for studying rat liver mitochondria and extracted mitochondrial lipids. Endothermic transition in the range 15–40°C was detected for the whole mitochondria and between 10–20°C for the extracted lipids.Acknowledgment. This work was supported in part by Volkswagen Foundation A.Z. 11-2711. 相似文献
18.
Structure, function and evolution of antifreeze proteins 总被引:16,自引:0,他引:16
Antifreeze proteins bind to ice crystals and modify their growth. These proteins show great diversity in structure, and they
have been found in a variety of organisms. The ice-binding mechanisms of antifreeze proteins are not completely understood.
Recent findings on the evolution of antifreeze proteins and on their structures and mechanisms of action have provided new
understanding of these proteins in different contexts. The purpose of this review is to present the developments in contrasting
research areas and unite them in order to gain further insight into the structure and function of the antifreeze proteins.
Received 2 September 1998; received after revision 21 October 1998; accepted 2 November 1998 相似文献
19.
Oxidative stress and hypoxia-like injury cause Alzheimer-type molecular abnormalities in central nervous system neurons 总被引:11,自引:0,他引:11
de la Monte SM Neely TR Cannon J Wands JR 《Cellular and molecular life sciences : CMLS》2000,57(10):1471-1481
Neuronal loss and neuritic/cytoskeletal lesions (synaptic disconnection and proliferation of dystrophic neurites) represent
major dementia-associated abnormalities in Alzheimer’s disease (AD). This study examined the role of oxidative stress as a
factor contributing to both the cell death and neuritic degeneration cascades in AD. Primary neuron cultures were treated
with H2O2 (9–90 μM) or desferrioxamine (2–25 μM) for 24 h and then analyzed for viability, mitochondrial mass, mitochondrial function,
and pro-apoptosis and sprouting gene expression. H2O2 treatment causes free-radical injury and desferrioxamine causes hypoxia-type injury without free radical generation. The
H2O2-treated cells exhibited sustained viability but neurite retraction, impaired mitochondrial function, increased levels of
the pro-apoptosis gene product CD95/Fas, reduced expression of N2J1-immunoreactive neuronal thread protein and synaptophysin,
and reduced distribution of mitochondria in neuritic processes. Desferrioxamine treatment resulted in dose-dependent neuronal
loss associated with impaired mitochondrial function, proliferation of neurites, and reduced expression of GAP-43, which has
a role in path-finding during neurite outgrowth. The results suggest that oxidative stress can cause neurodegeneration associated
with enhanced susceptibility to apoptosis due to activation of pro-apoptosis genes, neurite retraction (synaptic disconnection),
and impaired transport of mitochondria to cell processes where they are likely required for synaptic function. In contrast,
hypoxia-type injury causes neuronal loss with proliferation of neurites (sprouting), impaired mitochondrial function, and
reduced expression of molecules required to form and maintain synaptic connections. Since similar abnormalities occur in AD,
both oxidative stress and hypoxic injury can contribute to AD neurodegeneration.
Received 24 May 2000; received after revision 7 July 2000; accepted 27 July 2000 相似文献
20.
Lukas Trixl Thomas Amort Alexandra Wille Manuela Zinni Susanne Ebner Clara Hechenberger Felix Eichin Hanna Gabriel Ines Schoberleitner Anming Huang Paolo Piatti Roxana Nat Jakob Troppmair Alexandra Lusser 《Cellular and molecular life sciences : CMLS》2018,75(8):1483-1497
Chemical modifications of RNA have been attracting increasing interest because of their impact on RNA fate and function. Therefore, the characterization of enzymes catalyzing such modifications is of great importance. The RNA cytosine methyltransferase NSUN3 was recently shown to generate 5-methylcytosine in the anticodon loop of mitochondrial tRNAMet. Further oxidation of this position is required for normal mitochondrial translation and function in human somatic cells. Because embryonic stem cells (ESCs) are less dependent on oxidative phosphorylation than somatic cells, we examined the effects of catalytic inactivation of Nsun3 on self-renewal and differentiation potential of murine ESCs. We demonstrate that Nsun3-mutant cells show strongly reduced mt-tRNAMet methylation and formylation as well as reduced mitochondrial translation and respiration. Despite the lower dependence of ESCs on mitochondrial activity, proliferation of mutant cells was reduced, while pluripotency marker gene expression was not affected. By contrast, ESC differentiation was skewed towards the meso- and endoderm lineages at the expense of neuroectoderm. Wnt3 was overexpressed in early differentiating mutant embryoid bodies and in ESCs, suggesting that impaired mitochondrial function disturbs normal differentiation programs by interfering with cellular signalling pathways. Interestingly, basal levels of reactive oxygen species (ROS) were not altered in ESCs, but Nsun3 inactivation attenuated induction of mitochondrial ROS upon stress, which may affect gene expression programs upon differentiation. Our findings not only characterize Nsun3 as an important regulator of stem cell fate but also provide a model system to study the still incompletely understood interplay of mitochondrial function with stem cell pluripotency and differentiation. 相似文献