Effects of an acetyl-coenzyme A carboxylase inhibitor and a sodium-sparing diuretic on aldosterone-stimulated sodium transport, lipid synthesis, and phospholipid fatty acid composition in the toad urinary bladder

Lien, Eric L.; Goodman, David B. P.; Rasmussen, Howard

doi:10.1021/bi00683a030

Cited by 55 publications

(13 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…If citrate synthase is rate-limiting for ATP synthesis at the site ofmineralocorticoid action (distal segment of the nephron), modulation of the available ATP/ADP could alter both Na § conductance and active Na § transport [6,20]. Alternatively, the effects of aldosterone on citrate synthase and other mitochondrial proteins could modify lipid metabolism and various transport functions as proposed by Lien et al [18].…”

Section: Discussionmentioning

confidence: 99%

Induction of citrate synthase by aldosterone in the rat kidney

Law

Edelman

1978

J. Membrain Biol.

View full text Add to dashboard Cite

The possible induction of renal citrate synthase (E.C. 4.1.3.7) by aldosterone was evaluated in the adrenalectomized rat. Three hours after administration of aldosterone (0.8 microgram/100 g body wt), renal cortical and medullary citrate synthase activity was significantly increased as reported previously by Kinne and Kirsten (Kinne, R., Kirsten, R. 1968. Pfleugers Arch. 300:244). In contrast, no change in this activity was detected in the renal papilla or the liver, under the same conditions. Kinetic analysis revealed that injection of aldosterone had no effect on the KmS for acetyl-CoA and oxalacetate but augmented Vmax of renal medullary citrate synthase activity by 40%. The aldosterone-dependent increase in medullary citrate synthase activity was proportionate to the associated increase in the quantity of antiserum (specific for citrate synthase) required for half-maximal immuno-precipitation. The possibility that aldosterone induced the synthesis of citrate synthase was evaluated in two sets of experiments. In the first set, adrenalectomized rats were injected intraperitoneally with either aldosterone (0.8 microgram/100 g body wt) or the diluent, and simultaneously with 3H or 35S methionine (500 muCi/rat). The isotopes were reversed in about half of the experiments. Three hours after the injection, renal citrate synthase was isolated by ATP-sepharose column chromatography and immuno-precipitation with the specific antiserum. Aldosterone augmented methionine incorporation into renal citrate synthase by 55% but had no effect on incorporation into the hepatic enzyme. In the second set, adrenalectomized rats were injected with either aldosterone (0.8 microcram/100 g body wt) or the diluent, the kidneys were removed 1 hr later and medullary slices were incubated in either 3H- or 35S-methionine at 20 degrees for 2 hr. Mitochondrial citrate synthase was isolated either by ATP-sepharose column chromatography and immuno-precipitation, or by polyacrylamide gel electrophoresis. Aldosterone increased methionine incorporation into the immuno-precipitates by 30% and into the enzyme peak resolved by polyacrylamide gel electrophoresis by 43%. The latter increase was eliminated by prior administration of either actinomycin D (70--80 microgram/100 g body wt) or spirolactone (SC-26304) (80 microgram/100 g body wt). An equimolar dose of dexamethasone (0.8 microgram/100 g body wt) had no effect on the isotope ratio associated with citrate synthase activity in the polyacrylamide gels.

show abstract

Section: Discussionmentioning

confidence: 99%

Induction of citrate synthase by aldosterone in the rat kidney

Law

Edelman

1978

J. Membrain Biol.

View full text Add to dashboard Cite

show abstract

“…Evidence has been accumulated to support the hypothesis that this physiological response is mediated by alterations in membrane lipid turnover and structure (7,8,32,33). Aldosterone treatment results in a stimulation of endogenous phospholipase activity and enhanced fatty acid synthesis and acyl transferase activity.…”

mentioning

confidence: 98%

Glyoxylate cycle in toad urinary bladder: possible stimulation by aldosterone.

Goodman¹,

Davis²,

Jones³

1980

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

(5,6). The two decarboxylative steps in the tricarboxylic acid cycle (isocitrate dehydrogenase and a-ketoglutarate dehydrogenase) can be bypassed and two-carbon units (acetyl-CoA) can be converted to four-carbon acids (succinate) instead of being oxidized to CO2 (Fig. 1).In previous studies of aldosterone action in the toad urinary bladder, we demonstrated that the hormone-induced increase in sodium transport is preceded by stimulation of endogenous phospholipase activity, increased phospholipid fatty acid synthesis, and the recycling of [14C]acetyl-CoA derived from several 1-14C-labeled fatty acids. This [14C]acetyl-CoA did not appear to be derived from mitochondrial /3-oxidation because aldosterone stimulated a generalized increase in phospholipid fatty acid specific activities without altering fatty acid oxidation, measured by [14C]CO2 production, during the first 30 min of exposure to hormone (7,8). Consequently, we have investigated the possibility that nonmitochondrial fatty acid metabolism might be altered by aldosterone in the toad urinary bladder.Our results indicate that the toad urinary bladder is capable of cyanide-insensitive fatty acid oxidation. More importantly, the tissue possesses the two enzymatic activities unique to the glyoxylate cycle. These two enzymes have been reported previously only in unicellular organisms, certain nematodes, and higher plants (9-13). In toad urinary bladder, fatty acid can serve as a gluconeogenic substrate; in the presence of aldosteThe publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U. S. C. §1734 solely to indicate this fact. 1521 rone, glycogen levels are higher. These data indicate that the toad urinary bladder is unique among higher animal tissues in that it has the enzymes necessary for the synthesis of carbohydrate from fatty acid. MATERIALS AND METHODSLarge female toads (Bufo marinus) were obtained from National Reagents (Bridgeport, CT). Hemibladders were removed from doubly pithed animals and incubated in an amphibian Ringer's solution (14). For enzyme assays, epithelial cells were scraped from 10-12 hemibladders and washed twice in a calcium-free amphibian Ringer's solution. To prepare a cell extract the cell pellet was frozen and thawed five times in calcium-free buffer and a 33% (wt/vol) homogenate was prepared in a Potter-Elvehjem homogenizer. The homogenate was then centrifuged at 3000 X g for 20 min at 4°C and the supernatant was used as the cell extract.Palmitoyl-CoA oxidation was assayed by the spectrophotometric reduction of NAD at 340 nm (15 from acetyl-CoA to be converted to four-carbon acids, bypassing the decarboxylative steps in the citric acid cycle.

show abstract

“…In addition to its well-established effect on protein metabolism (Edelman et al, 1963), it has now been well-documented that aldosterone has a pronounced effect on cell membrane lipid metabolism in the toad bladder (Goodman et al, 1971, q975;Lien et al, 1975Lien et al, , 1976. The one cell structure that is at particular risk from free radical damage is the cell membrane, in particular the membrane lipids (transmembrane proteins containing oxidizable amino acids are also susceptible to free-radical damage).…”

Section: Discussionmentioning

confidence: 99%

The ultrastructural immunocytochemical localization of superoxide dismutase in the amphibian urinary bladder: Effect of aldosterone

et al. 1989

Self Cite

View full text Add to dashboard Cite

Transmission electron microscopy and immunohistochemistry, the latter employing the avidin-biotin-peroxidase (ABC complex) technique, were utilized to localize copper-zinc superoxide dismutase (CuZn-SOD) enzyme activity in the epithelial cells of the toad urinary bladder mucosa. This 'scavenger' enzyme catalyses the dismutation (reduction-oxidation) of the superoxide anion (O2-), a toxic free radical generated during normal cellular respiration. In unstimulated epithelial cells, enzyme activity was seen in the cytosol of granular, mitochondrial-rich and goblet cells. The basal cells were generally devoid of enzyme activity. In addition to the cytosol, SOD activity was also seen in association with the apical plasma membrane of the epithelial cells. In the presence of the steroid hormone aldosterone (10(-7)M, 30 min-6h), CuZn-SOD activity was markedly increased along the luminal mucosal membrane of granular, mitochondrial-rich and goblet cells. This increase was seen as early as 30 min after the addition of hormone, and as long as 6h after treatment. The cytosolic reaction was usually decreased or absent under these conditions. From the data presented, it appears that CuZn-SOD is involved in electrolyte (sodium) transport in the epithelial cells of the toad urinary bladder. The latter may involve hormone-induced alterations in luminal cell membrane structure and chemistry.

show abstract

Effects of an acetyl-coenzyme A carboxylase inhibitor and a sodium-sparing diuretic on aldosterone-stimulated sodium transport, lipid synthesis, and phospholipid fatty acid composition in the toad urinary bladder

Cited by 55 publications

References 27 publications

Induction of citrate synthase by aldosterone in the rat kidney

Induction of citrate synthase by aldosterone in the rat kidney

Glyoxylate cycle in toad urinary bladder: possible stimulation by aldosterone.

The ultrastructural immunocytochemical localization of superoxide dismutase in the amphibian urinary bladder: Effect of aldosterone

Contact Info

Product

Resources

About