Differences in cholesterol oxidation and biosynthesis in liver of male and female rats

1961 ◽  
Vol 200 (3) ◽  
pp. 519-522 ◽  
Author(s):  
David Kritchevsky ◽  
Ezra Staple ◽  
Joseph L. Rabinowitz ◽  
Michael W. Whitehouse
Keyword(s):  
Rat Liver ◽  
Sodium Acetate ◽  
Liver Mitochondria ◽  
Female Rats ◽  
Male Rats ◽  
Cholesterol Oxidation ◽  
Male Rat ◽  
Rat Liver Mitochondria ◽  
Oxidized Cholesterol ◽  
Liver Homogenates

Female rat liver mitochondria oxidized cholesterol-26-C14 and sodium pyruvate-2-C14 to C14O2 to a much greater extent (per mg N) than did male rat liver mitochondria. Mitochondrial preparations from livers of castrated, estrogenized or castrated-estrogenized male rats all oxidized cholesterol-26-C14 to a greater extent than did liver preparations from normal male rats. No differences were observed in the oxidation of sodium octanoate-1-C14. The serum and liver cholesterol levels of the feminized rats were higher than those of the intact males. Biosynthesis of cholesterol from sodium acetate-2-C14 by male rat liver homogenates was significantly lower than biosynthesis by liver homogenates from normal female rats or gonadectomized rats of both sexes. The rate of biosynthesis from mevalonic acid-2-C14 by liver homogenates from castrated male rats was much higher than in homogenates of oophorectomized females or intact males or females. Differences in sex or gonadectomy had no effect on biosynthesis of fatty acids from sodium acetate-2-C14.

scholarly journals Increased bioactivation of dihaloalkanes in rat liver due to induction of class Theta glutathione S-transferase T1-1

1998 ◽  
Vol 335 (3) ◽  
pp. 619-630 ◽  
Author(s):  
Philip J. SHERRATT ◽  
Margaret M. MANSON ◽  
Anne M. THOMSON ◽  
Erna A. M. HISSINK ◽  
Gordon E. NEAL ◽  
...  
Keyword(s):  
Western Blotting ◽  
Rat Liver ◽  
Female Rats ◽  
Male Rats ◽  
Male Rat ◽  
Female Rat ◽  
Glutathione S Transferase ◽  
Chemopreventive Agents ◽  
Cytoplasmic Staining ◽  
Potent Inducer

A characteristic feature of the class Theta glutathione S-transferase (GST) T1-1 is its ability to activate dichloromethane and dibromoethane by catalysing the formation of mutagenic conjugates. The level of the GSTT1 subunit within tissues is an important determinant of susceptibility to the carcinogenic effects of these dihaloalkanes. In the present study it is demonstrated that hepatic GST activity towards these compounds can be elevated significantly in female and male Fischer-344 rats by feeding these animals on diets supplemented with cancer chemopreventive agents. Immunoblotting experiments showed that increased activity towards the dihaloalkanes is associated with elevated levels of the GSTT1 subunit in rat liver. Sex-specific effects were observed in the induction of GSTT1 protein. Amongst the chemopreventive agents tested, indole-3-carbinol proved to be the most potent inducer of hepatic GSTT1 in male rats (6.2-fold), whereas coumarin was the most potent inducer of this subunit in the livers of female rats (3.5-fold). Phenobarbital showed significant induction of GSTT1 only in male rat liver and had little effect in female rat liver. Western blotting showed that class Alpha, Mu and Pi GST subunits are not co-ordinately induced with GSTT1, indicating that the expression of GSTT1 is determined, at least in part, by mechanisms distinct from those that regulate levels of other transferases. The increase in amount of hepatic GSTT1 protein was also reflected by an increase in the steady-state level of mRNA in response to treatment with chemopreventive agents and model inducers. Immunohistochemical detection of GSTT1 in rat liver supported the Western blotting data, but showed, in addition to cytoplasmic staining, significant nuclear localization of the enzyme in hepatocytes from some treated animals, including those fed on an oltipraz-containing diet. Significantly, the hepatic level of cytochrome P-450 2E1, an enzyme which offers a detoxification pathway for dihaloalkanes, was unchanged by the various inducing agents studied. It is concluded that the induction of GSTT1 by dietary components and its localization within cells are important factors that should be considered when assessing the risk dihaloalkanes pose to human health.

Modulation of oxidative phosphorylation machinery signifies a prime mode of anti-ageing mechanism of calorie restriction in male rat liver mitochondria

2009 ◽  
Vol 11 (3) ◽  
pp. 321-334 ◽  
Author(s):  
Diksha Dani ◽  
Isao Shimokawa ◽  
Toshimitsu Komatsu ◽  
Yoshikazu Higami ◽  
Uwe Warnken ◽  
...  
Keyword(s):  
Oxidative Phosphorylation ◽  
Rat Liver ◽  
Calorie Restriction ◽  
Liver Mitochondria ◽  
Male Rat ◽  
Rat Liver Mitochondria

scholarly journals Studies on the biosynthesis of protein and lipid components of rat liver mitochondria

1967 ◽  
Vol 105 (2) ◽  
pp. 605-609 ◽  
Author(s):  
C B Taylor ◽  
E. Bailey ◽  
W Bartley
Keyword(s):  
Rat Liver ◽  
Soluble Protein ◽  
Specific Radioactivity ◽  
Liver Mitochondria ◽  
Protein Fractions ◽  
Male Rats ◽  
Rat Liver Mitochondria ◽  
Insoluble Protein ◽  
Lipid Components

1. Male rats were injected intraperitoneally with l-[35S]methionine, [32P]-phosphate and [2−14C]acetate. The animals were killed at various times up to 72hr. after injection, and liver mitochondria were prepared and fractionated into soluble protein, insoluble protein and lipid for assay of the radioactivity of each fraction. 2. The maximal specific radioactivity of total mitochondrial phospholipid with respect to both 32P and 14C was attained after approx. 6hr. 3. 32P was incorporated most rapidly into phosphatidylethanolamine, maximal incorporation being attained after approx. 6hr.; maximal incorporation into lecithin occurred after 6–12hr. The specific radioactivity of cardiolipin was still slowly increasing at the end of the experiment (72hr.). 4. There were no major differences between the rates of incorporation of 14C into the lecithin, phosphatidylethanolamine and cardiolipin fractions of mitochondrial phospholipid, maximal incorporation in each case occurring after approx. 6hr. 5. Maximal incorporation of 35S into both soluble and insoluble protein fractions was attained less than 12hr. after injection, the maximal specific radioactivity of soluble protein being higher than that of insoluble protein.

scholarly journals Studies on the activation of rat liver pyruvate dehydrogenase and 2-oxoglutarate dehydrogenase by adrenaline and glucagon. Role of increases in intramitochondrial Ca2+ concentration

1985 ◽  
Vol 231 (3) ◽  
pp. 597-608 ◽  
Author(s):  
J G McCormack
Keyword(s):  
Rat Liver ◽  
Pyruvate Dehydrogenase ◽  
Liver Mitochondria ◽  
Active Enzyme ◽  
Female Rats ◽  
Rat Liver Mitochondria ◽  
Na Ions ◽  
Oxoglutarate Dehydrogenase

The administration in vivo of either adrenaline or glucagon alone resulted in increases of about 2-fold in the amounts of active, non-phosphorylated, pyruvate dehydrogenase in the livers of fed male or female rats, whereas when administered together increases of about 4-fold were obtained. Ca2+-dependent increases in the amount of active enzyme of up to about 5-fold could be achieved in isolated rat liver mitochondria by incubating them with increasing extramitochondrial [Ca2+]; from this, two conditions of Ca loading were chosen which caused increases in active enzyme similar to those with the hormone treatments given above. The increases in enzyme activity owing to these Ca loads persisted through the ‘re-isolation’ of mitochondria and their incubation in Na+-free KCl-based media containing EGTA. Differences from values obtained with unloaded controls could be diminished by adding Na+ ions to cause the egress of Ca2+ from the mitochondria, or enough extramitochondrial Ca2+ to saturate the enzyme in its Ca2+-dependent activation; the effects of Na+ could be blocked by diltiazem, an inhibitor of mitochondrial Na+/Ca2+ exchange. The re-isolated, Ca-preloaded, mitochondria also exhibited enhanced activities of 2-oxoglutarate dehydrogenase when assayed at non-saturating [2-oxoglutarate] by two different methods; effects of Na+, Ca2+ or diltiazem on the persistent activations of this enzyme were similar to those for pyruvate dehydrogenase. Na+ caused a marked depletion, which could be blocked by diltiazem, of the 45Ca content of re-isolated mitochondria which had pre-loaded with Ca, containing 45Ca, to the same degrees as above. The activities of pyruvate dehydrogenase and 2-oxoglutarate dehydrogenase in incubated liver mitochondria prepared from rats subjected to the hormone treatments given above were found to behave in a very similar manner to those exhibited in the re-isolated, Ca-preloaded, mitochondria. It is concluded that these hormones each bring about the activations of these rat liver enzymes by causing increases in intramitochondrial [Ca2+], and that their effects, as such, are additive.

scholarly journals Effect of age, gonadectomy and hypophysectomy on mitochondrial hydroxylation of vitamin D3 (cholecalciferol) and of 5β-cholestane-3α,7α,12α-triol in female and male rat liver

1988 ◽  
Vol 251 (2) ◽  
pp. 475-481 ◽  
Author(s):  
K Saarem ◽  
J I Pedersen
Keyword(s):  
Sex Hormones ◽  
Rat Liver ◽  
Vitamin D3 ◽  
Female Rats ◽  
Male Rats ◽  
Male Rat ◽  
Side Chain ◽  
Hydroxylase Activity ◽  
Testosterone Treatment ◽  
Alpha 7

In a previous study we found that liver mitochondrial side-chain hydroxylation of vitamin D3 (cholecalciferol) and of 5 beta-cholestane-3 alpha,7 alpha,12 alpha-triol was higher in female than in male rats [Saarem & Pedersen (1987) Biochem. J. 247, 73-78]. The present paper describes the effects of age, gonadectomy and hypophysectomy on these activities. The sex difference became manifest above the age of 7 weeks. Ovariectomy and/or injection of oestradiol valerate had no effect on the hydroxylase activities in adult females. Castration increased, and subsequent testosterone treatment decreased, the hydroxylase activities in adult males. Hypophysectomy had no effect in females, but increased the hydroxylase activities in males. Testosterone treatment had no effect in hypophysectomized females or males. Injection of oestradiol valerate had no effect on the hydroxylase activities in hypophysectomized females. In hypophysectomized males this treatment had no effect on the vitamin D3 25-hydroxylase activity, but decreased the C27-steroid 27-hydroxylase activity in males. Microsomal 1 alpha-hydroxyvitamin D3 25-hydroxylase activity was lower in females than in males in all age groups. Castration or hypophysectomy decreased the activity in male rats. It is concluded that, in adult female rats, the mitochondrial side-chain hydroxylation of vitamin D3 and of 5 beta-cholestane-3 alpha,7 alpha,12 alpha-triol is independent of sex hormones. In males these activities are regulated by influence of sex hormones on the hypophysis, probably by the presence of androgens in the neonatal period. Different effects on the two hydroxylases indicate the presence of at least two different cytochromes P-450 in rat liver mitochondria.

scholarly journals Heparprotective effect of Bergenia crassifolia extract and silymarinat experimental inhibition of β-oxidation of fatty acids causedby 4-pentenioc acid

2007 ◽  
Vol 6 (4) ◽  
pp. 64-70
Author(s):  
D. V. Shutov
Keyword(s):  
Fatty Acids ◽  
Rat Liver ◽  
Energy Production ◽  
Liver Mitochondria ◽  
Male Rats ◽  
Rat Liver Mitochondria ◽  
Metabolic States ◽  
Rate Of Oxygen Consumption ◽  
Energy Production System ◽  
Bergenia Crassifolia

The object of this research was to study rat liver bioenergetics at pathology caused by inhibition of β-oxidation of fatty acids against the background of 4-pentenoic acid injection and at silymarin and Bergenia crassifolia extract therapy. The experiment was conducted with 50 nonpedigreed male rats. The functional state of the energy production system was estimated by the polarogaphic method from the rate of oxygen consumption in different Chans metabolic states. At silymarin therapy, increase was observed in the oxidative phosphorylation coupling in all metabolic states. The Bergenia crassifolia extract favored normalization of energy production parameters in rat liver mitochondria more efficiently than silymarint did.

scholarly journals The redox state of the nicotinamide–adenine dinucleotides in rat liver homogenates

1968 ◽  
Vol 108 (4) ◽  
pp. 513-520 ◽  
Author(s):  
H. A. Krebs ◽  
T. Gascoyne
Keyword(s):  
Rat Liver ◽  
Redox State ◽  
Liver Mitochondria ◽  
Rat Liver Mitochondria ◽  
Redox States ◽  
Cell Compartments ◽  
Dehydrogenase System ◽  
Liver Homogenates ◽  
Saline Medium ◽  
Pyruvate Ratio

1. The redox state of the NAD couple of rat liver mitochondria, as measured by the [β-hydroxybutyrate]/[acetoacetate] ratio, rapidly changed in the direction of oxidation during the preparation of homogenates in a saline medium. The value of the [β-hydroxybutyrate]/[acetoacetate] ratio fell from 2·3 to 0·15 in 10min. EDTA diminished the fall and succinate prevented it. 2. The redox state of the rat liver cytoplasm, as measured by the [lactate]/[pyruvate] ratio, changed slightly in the direction of reduction during the preparation of homogenate. This was prevented by succinate. 3. In unsupplemented homogenates the differences in the redox states of mitochondria and cytoplasm decreased. Succinate and EDTA together maintained the differences within the physiological range. A measure of the ability of the mitochondria to maintain different redox states in mitochondria and cytoplasm is the value of the expression [lactate][acetoacetate]/[pyruvate][β-hydroxybutyrate]. If there are no differences in the redox states of the NAD in the two cell compartments the value of the expression is 444 at 37°. The value in the intact rat liver is between 4·7 and 21. 4. α-Oxoglutarate or glutamate were still more effective than succinate in maintaining high [β-hydroxybutyrate]/[acetoacetate] ratios in the homogenates because these substrates supply a reducing agent of NAD+ and, through succinate, an inhibitor of the oxidation of NADH. 5. When supplemented with α-oxoglutarate and EDTA, homogenates readily adjust the redox state of the β-hydroxybutyrate dehydrogenase system after it has been upset by the addition of either acetoacetate or β-hydroxybutyrate. 6. Amytal and rotenone raised the value of the [β-hydroxybutyrate]/[acetoacetate] ratio. This is taken to indicate that the reduction of acetoacetate in the homogenates was not an energy-linked process. 7. 2,4-Dinitrophenol shifted the [β-hydroxybutyrate]/[acetoacetate] ratio in the presence of succinate in favour of oxidation because it inhibited the oxidation of succinate and accelerated the oxidation of NADH. 8. Rotenone increased the rate of ketone-body formation of liver homogenates, though it decreased the rate of oxygen uptake.

scholarly journals Sex differences in the hydroxylation of cholecalciferol and of 5 β-cholestane-3 α, 7 α, 12 α-triol in rat liver

1987 ◽  
Vol 247 (1) ◽  
pp. 73-78 ◽  
Author(s):  
K Saarem ◽  
J I Pedersen
Keyword(s):  
Sex Hormones ◽  
Rat Liver ◽  
Female Rats ◽  
Regulatory Control ◽  
Male Rats ◽  
Male Rat ◽  
Female Rat ◽  
Significant Difference ◽  
Alpha 7 ◽  
Rat Livers

The effect of sex hormones on hydroxylation of cholecalciferol (‘vitamin D3’) and of 5 beta-cholestane-3 alpha, 7 alpha, 12 alpha-triol has been investigated in female- and male-rat livers. The mitochondrial cholecalciferol 25-hydroxylase and C27-steroid 27-hydroxylase activities were respectively 4.6- and 2.7-fold higher in female- than in male-rat livers. The microsomal 1 alpha-hydroxycholecalciferol 25-hydroxylase was 2.8-fold higher in male- than in female-rat liver. No significant difference was found in the microsomal 25-hydroxylation of 5 beta-cholestane-3 alpha, 7 alpha, 12 alpha-triol. Liver microsomes (microsomal fractions) from male, but not from female, rats also catalysed 1-hydroxylation of 5 beta-cholestane-3 alpha, 7 alpha, 12 alpha-triol. Injection of testosterone into female rats decreased the mitochondrial cholecalciferol 25-hydroxylase and C27-steroid 27-hydroxylase activities, but not to a statistically significant extent. Testosterone treatment had no effect on the microsomal hydroxylases in female-rat liver. Injection of oestradiol valerate to male rats resulted in increased activities of both mitochondrial hydroxylases to the same levels as those of control females, while the microsomal enzyme activities decreased. The present results indicate that sex hormones exert a regulatory control on the mitochondrial cholecalciferol 25-hydroxylase and C27-steroid 27-hydroxylase activities.

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