Effects of (+)-Octanoylcarnitine on Deoxyribonucleic Acid Synthesis in Regenerating Rabbit Liver

1982 ◽  
Vol 62 (3) ◽  
pp. 295-297 ◽  
Author(s):  
Toshio Nakatani ◽  
Kazuhiro Yasuda ◽  
Kazue Ozawa ◽  
Sadao Kawashima ◽  
Takayoshi Tobe

1. (+)-Octanoylcarnitine, a potent inhibitor of fatty acid oxidation, was infused intraportally into rabbits after 70% hepatectomy, and its effects on the rate of deoxyribonucleic acid (DNA) synthesis were examined. 2. The rate of DNA synthesis was markedly enhanced 48 h after hepatectomy. At this time, synthesis was decreased significantly by (+)-octanoylcarnitine. 3. It is suggested that fatty acid oxidation contributes to enhanced hepatic regeneration by elevating the decreased energy charge level [(ATP + 0.5ADP)/(ATP + ADP + AMP)] of the remnant liver.

2002 ◽  
Vol 30 (6) ◽  
pp. 1064-1070 ◽  
Author(s):  
D. G. Hardie ◽  
D. A. Pan

The AMP-activated protein kinase (AMPK) is a sensor of cellular energy charge and a ‘metabolic master switch’. When activated by ATP depletion, it switches off ATP-consuming processes, while switching on catabolic pathways that generate ATP. AMPK exists as heterotrimeric complexes comprising catalytic α subunits and regulatory β and γ subunits, each of which occurs as multiple isoforms. Rising AMP and falling ATP, brought about by various types of cellular stress (including exercise in skeletal muscle), stimulate the system in an ultrasensitive manner. Acetyl-CoA carboxylase (ACC) exists in mammals as two isoforms, termed ACC-1 and ACC-2 (also known as ACC-α and ACC-β). AMPK phosphorylates and inactivates both isoforms at the equivalent site. Knockout mice, and other approaches, suggest that the malonyl-CoA produced by ACC-2 is exclusively involved in regulation of fatty acid oxidation, whereas that produced by ACC-1 is utilized in fatty acid synthesis. Activation of AMPK by cellular stress or exercise therefore switches on fatty acid oxidation (via phosphorylation of ACC-2) while switching off fatty acid synthesis (via phosphorylation of ACC-1). The Drosophila melanogaster genome contains single genes encoding homologues of the α, β and γ subunits of AMPK (DmAMPK) and of ACC (DmACC). Studies in a Drosophila embryonal cell line show that DmAMPK is activated by stresses that cause ATP depletion (oligomycin, hypoxia or glucose deprivation) and that this is associated with phosphorylation of the site on DmACC equivalent to the AMPK sites on mammalian ACC-1 and ACC-2. This is abolished when expression of DmAMPK is ablated using an RNA interference approach, proving that DmAMPK is necessary for phosphorylation of DmACC in response to ATP depletion.


1978 ◽  
Vol 170 (1) ◽  
pp. 123-127 ◽  
Author(s):  
J A McGowan ◽  
N Fausto

Compared with normally fed animals, rats fed on a low-protein diet for 3 days exhibit a considerable delay in DNA synthesis after partial hepatectomy. In the regenerating livers of these animals (a) the timing of the first peak of ornithine decarboxylase activity is not altered and (b) the second peak of enzyme activity is delayed by a few hours, but polyamine concentrations are similar to those of normally fed rats. The results suggest that regardless of the possible effect of polyamines on DNA synthesis, the time course of ornithine decarboxylase activity appears to be independent of the onset of DNA replication in regenerating livers.


1979 ◽  
Vol 178 (3) ◽  
pp. 621-626 ◽  
Author(s):  
J F Burke ◽  
P M Duff ◽  
C K Pearson

In order to ascertain the identity of the DNA-dependent DNA polymerase responsible for the observed DNA synthesis in nuclei isolated from baby-hamster kidney (BHK-21/C13) cells a comparative study was carried out on the effects of some drugs, reported to influence DNA synthesis, on DNA synthesis catalysed by these nuclei and by partially purified DNA polymerase-alpha and -beta. In all cases DNA synthesis by isolated nuclei and polymerase-alpha was inhibited to similar extents by N-ethylmaleimide, p-hydroxymercuribenzoate, novobiocin, heparin and phosphonoacetic acid; polymerase-beta was much less affected by these compounds. Ethidium bromide inhibited all DNA synthesis to similar extents, although at low concentrations (about 2 microgram/ml) synthesis in isolated nuclei was stimulated. The results are discussed in relation to the proposal that DNA polymerase-alpha catalyses the covalent extension of Okazaki fragments that these nuclei carry out in vitro.


Endocrinology ◽  
2001 ◽  
Vol 142 (1) ◽  
pp. 229-240 ◽  
Author(s):  
Sharon P. Cousin ◽  
Sigrun R. Hügl ◽  
Christian E. Wrede ◽  
Hiroshi Kajio ◽  
Martin G. Myers ◽  
...  

1971 ◽  
Vol 121 (5) ◽  
pp. 803-809 ◽  
Author(s):  
M. A. Waqar ◽  
L. A. Burgoyne ◽  
M. R. Atkinson

The properties of a nuclear preparation from rat liver and thymus are described. (1) Nearest-neighbour analysis after incorporation of 32P-labelled nucleotide residues from dATP, dCTP, dGTP, dTTP and arabinofuranosyl analogues of CTP and ATP shows template-dependent DNA synthesis. (2) Where primer termini are limiting, incorporation of arabinofuranosyl analogues of AMP and CMP residues proceeds to a limit indicating that both of these analogues are DNA chain terminators. (3) No large differences have been found between the priming potentialities or the intrinsic DNA polymerase activities of nuclei from resting or regenerating liver and the relationship of this DNA synthesis in vitro to DNA replication or repair in vivo is briefly discussed.


1963 ◽  
Vol 41 (11) ◽  
pp. 2343-2351 ◽  
Author(s):  
S. Mak ◽  
J. E. Till

The use of isotopically labeled 5-iodo-2′-deoxyuridine (I125UdR) for determination of the rate of deoxyribonucleic acid synthesis in mammalian cells in vitro has been investigated. The results obtained indicate that for this purpose I125UdR is a suitable substitute for the more commonly used DNA precursor, tritium-labeled thymidine (H3TdR). I125UdR appears to be incorporated specifically into the DNA of cells in culture, and has been demonstrated to compete with H3TdR, although the Km for H3TdR was smaller than that of I125UdR by a factor of approximately 4. The amount of label incorporated into DNA of cells increased linearly with time. When the rate of DNA synthesis was reduced by exposure of the cells to various doses of X-rays, the ratio of I125UdR incorporation to H3TdR incorporation into DNA of cells was found to be a constant, which supports the view that uptake of the analogue provides as reliable an indication of effects upon the rate of DNA synthesis as does that of H3TdR. The chief advantage of I125UdR over H3TdR is that I125 is a gamma emitter, so that the difficulties encountered in detection of the low energy beta particles from H3 may be avoided.


2012 ◽  
Vol 108 (11) ◽  
pp. 1980-1993 ◽  
Author(s):  
Takashi Ide ◽  
Yoshiko Ono ◽  
Hiroshi Kawashima ◽  
Yoshinobu Kiso

Interrelated effects of dihomo-γ-linolenic acid (DGLA) and arachidonic acid (ARA), and sesamin, a sesame lignan, on hepatic fatty acid synthesis and oxidation were examined in rats. Rats were fed experimental diets supplemented with 0 or 2 g/kg sesamin (1:1 mixture of sesamin and episesamin), containing 100 g/kg of maize oil or fungal oil rich in DGLA or ARA for 16 d. Among the groups fed sesamin-free diets, oils rich in DGLA or ARA, especially the latter, compared with maize oil strongly reduced the activity and mRNA levels of various lipogenic enzymes. Sesamin, irrespective of the type of fat, reduced the parameters of lipogenic enzymes except for malic enzyme. The type of dietary fat was rather irrelevant in affecting hepatic fatty acid oxidation among rats fed the sesamin-free diets. Sesamin increased the activities of enzymes involved in fatty acid oxidation in all groups of rats given different fats. The extent of the increase depended on the dietary fat type, and the values became much higher with a diet containing sesamin and oil rich in ARA in combination than with a diet containing lignan and maize oil. Analyses of mRNA levels revealed that the combination of sesamin and oil rich in ARA compared with the combination of lignan and maize oil markedly increased the gene expression of various peroxisomal fatty acid oxidation enzymes but not mitochondrial enzymes. The enhancement of sesamin action on hepatic fatty acid oxidation was also confirmed with oil rich in DGLA but to a lesser extent.


1961 ◽  
Vol 11 (2) ◽  
pp. 311-319 ◽  
Author(s):  
Yasuo Hotta ◽  
Herbert Stern

Microspores isolated from Lilium longiflorum and Trillium erectum were studied with respect to their capacities for phosphorylating deoxyribosides in vitro. It was found that such capacities are manifest only during brief intervals of time adjacent to periods of DNA synthesis, and that none of the neighboring cells in the anther acquire them. The observed patterns of behavior are interpreted in terms of enzyme induction as a device for regulating DNA synthesis.


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