Invivo modification of the energy charge in the liver cell

Sánchez, Victoria Chagoya de; Brunner, Aurora; Piña, Enrique

doi:10.1016/s0006-291x(72)80138-4

Cited by 56 publications

(15 citation statements)

References 4 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Adenosine was employed in the present study as a systemic quasi-ionophore for Pi. As might have been predicted (45)(46)(47)(48), adenosine administered alone induced hypophosphatemia and a 40% increase in both the hepatic and renal cortical concentrations of adenine nucleotides, the increase being predominantly as ATP (and unassociated with a reduction of Pi in these tissues). It was reckoned that the nucleotides comprising this increment would release otherwise unavailable Pi within the cells of the liver and renal cortex when these tissues either hydrolysed ATP or degraded AMP and its deamination product, inosine 5'-monophosphate, to inosine, reactions presumed to proceed at increased rates with fructose loading (16)(17)(18)(19)(20)(21)(22)(23).…”

Section: Control Studiessupporting

confidence: 59%

Evidence that the Severity of Depletion of Inorganic Phosphate Determines the Severity of the Disturbance of Adenine Nucleotide Metabolism in the Liver and Renal Cortex of the Fructose-Loaded Rat

Morris¹,

Nigon²,

Reed³

1978

J. Clin. Invest.

View full text Add to dashboard Cite

A B S T R A C T To test the hypothesis that in both the liver and renal cortex ofthe fructose-loaded rat, severity of depletion of inorganic phosphate (Pi), and not the magnitude of accumulation of fructose-l-phosphate (F-1-P), determines the severity of the dose-dependent reduction of ATP, we intraperitoneally injected fed rats with fructose, 20 and 40 umol/g, alone, and at the higher load, in combination with (a) sodium phosphate, 20 umol/g, administered shortly beforehand or subsequently or, (b) adenosine, 2 ,umol/g, administered beforehand. The following observations were made: (a) With fructose loading alone, at the higher load, both Pi and total adenine nucleotides (TAN) were reduced by one third in the renal cortex and (as previously observed) by two thirds in the liver; and at either load, the reduction of ATP (and TAN)

show abstract

Section: Control Studiessupporting

confidence: 59%

Evidence that the Severity of Depletion of Inorganic Phosphate Determines the Severity of the Disturbance of Adenine Nucleotide Metabolism in the Liver and Renal Cortex of the Fructose-Loaded Rat

Morris¹,

Nigon²,

Reed³

1978

J. Clin. Invest.

View full text Add to dashboard Cite

show abstract

“…The derivative IFC-305 has a longer half-life in the liver potentiating the beneficial effects of adenosine on CCl 4 -induced cirrhosis in rats [10]. Adenosine presents interesting effects in hepatic metabolism: it increases the energy charge of the hepatocyte, augments the synthesis of hepatic glycogen, and inhibits fatty acid oxidation [11–13]; it also modulates the redox state of the cell through maintaining the structure and function of the mitochondria [14]. In acute hepatotoxicity, induced by ethanol or CCl 4 , adenosine prevents the fatty liver induced by the toxics, restitutes the energetic balance, the redox equilibrium, mitochondrial function, and prevents oxidative stress by diminishing the reactive oxygen species and increasing antioxidant defenses [5, 15–18].…”

Section: Introductionmentioning

confidence: 99%

Recovery of the Cell Cycle Inhibition inCCl4-Induced Cirrhosis by the Adenosine Derivative IFC-305

Sánchez

Martínez-Pérez

Hernández‐Muñoz

et al. 2012

International Journal of Hepatology

Self Cite

View full text Add to dashboard Cite

Introduction. Cirrhosis is a chronic degenerative illness characterized by changes in normal liver architecture, failure of hepatic function, and impairment of proliferative activity. The aim of this study is to know how IFC-305 compound induces proliferation of the liver during reversion of cirrhosis. Methods. Once cirrhosis has been installed by CCl4 treatment for 10 weeks in male Wistar rats, they were divided into four groups: two received saline and two received the compound; all were euthanized at 5 and 10 weeks of treatment. Liver homogenate, mitochondria, and nucleus were used to measure cyclins, CDKs, and cell cycle regulatory proteins PCNA, pRb, p53, E2F, p21, p27, HGF, liver ATP, and mitochondrial function. Results. Diminution and small changes were observed in the studied proteins in the cirrhotic animals without treatment. The IFC-305-treated rats showed a clear increase in most of the proteins studied mainly in PCNA and CDK6, and a marked increased in ATP and mitochondrial function. Discussion/Conclusion. IFC-305 induces a recovery of the cell cycle inhibition promoting recovery of DNA damage through the action of PCNA and p53. The increase in energy and preservation of mitochondrial function contribute to recovering the proliferative function.

show abstract

“…An increase in hepatic ATP and total adenine nucleotides has been documented after the administration of adenosine to intact rats (1) and after the addition of the nucleoside to the perfusion medium of the isolated rat liver (2) or to suspensions of isolated rat hepatocytes (3,4). The present work was undertaken in order to study the influence of this enlargement of the adenine nucleotide pool on the rate of its degradation.…”

mentioning

confidence: 99%

“…Coformycin {(R)-3-(f3-D-erythropentofuranosyl)-3, 6, 7, 8-tetrahydroimidazo [4,5-d] [1,3]diazepin-8-ol} was a gift of H. Umezawa (Institute of Microbial Chemistry, Tokyo, Japan). 5-Iodotubercidin {4-amino-5-iodo-7-(3-D-ribofuranosyl)pyrrolo [2,3-d]pyrimidine; ITu} was provided by L. B. Townsend, (University of Michigan College of Pharmacy, Ann Arbor, MI).…”

mentioning

confidence: 99%

Evidence for a substrate cycle between AMP and adenosine in isolated hepatocytes.

Bontemps¹,

Berghe²,

Hers³

1983

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

106

View full text Add to dashboard Cite

The effect of adenosine on the metabolism of prelabeled adenine nucleotides was investigated in isolated hepatocytes. Adenosine caused an :2-fold increase in the ATP content of the cells. This effect was in part counteracted by an increased rate of adenine nucleotide catabolism that could be explained by a stimulation of both AMP deaminase (AMP aminohydrolase, EC 3.5.4.6) and the cytoplasmic 5'-nucleotidase (5'-ribonucleotide phosphohydrolase, EC 3.1.3.5) because of the increased concentration of ATP. The unexpected finding that labeled adenosine was formed immediately after the addition of the unlabeled nucleoside could be explained by the trapping effect of adenosine. An accumulation of labeled adenosine was observed also in the presence of 5-iodotubercidin, a potent inhibitor of adenosine kinase (ATP:adenosine 5'-phosphotransferase, EC 2.7.1.20). Under these conditions, there was a decrease in the concentration of ATP in the cell and a 2-to 3-fold increase in the rate of formation of allantoin. This formation of adenosine was only slightly decreased by inhibition of the membranous 5'-nucleotidase; it led to the accumulation of S-adenosylhomocysteine in the presence of coformycin and an excess of L-homocysteine. It was concluded that, under basal conditions, the cytoplasmic 5'-nucleotidase present in the liver cell continuously produces adenosine, which is immediately reconverted into AMP by adenosine kinase, without giving rise to allantoin. This futile cycle between AMP and adenosine amounts to at least 20 nmol/min per g of liver and, thus, exceeds the basic rate of allantoin formation.An increase in hepatic ATP and total adenine nucleotides has been documented after the administration of adenosine to intact rats (1) and after the addition of the nucleoside to the perfusion medium of the isolated rat liver (2) or to suspensions of isolated rat hepatocytes (3,4). The present work was undertaken in order to study the influence of this enlargement of the adenine nucleotide pool on the rate of its degradation. Indeed, no mechanism as yet is known that would adapt the rate of adenine nucleotide catabolism to an increased rate of synthesis. We came previously to the conclusion that AMP deaminase (AMP aminohydrolase, EC 3.5.4.6) constitutes the limiting enzyme of hepatic adenine nucleotide catabolism under basal conditions and that deinhibition of this enzyme accounts for the increased formation of purine catabolites observed after the administration of fructose or in anoxia (see ref. 5 for a review). This conclusion was based on work with partially purified enzymes (6, 7) and was confirmed by studies in isolated hepatocytes (8, 9). The adenine nucleotides were labeled with [14C]adenine, and their catabolism was investigated by following the appearance of the radioactivity in their breakdown products. By using the same technique, we now have reached the conclusion that the activity of AMP deaminase is stimulated in the conditions prevailing in the liver cell after the administration of adenosine. Furthermo...

show abstract

Invivo modification of the energy charge in the liver cell

Cited by 56 publications

References 4 publications

Evidence that the Severity of Depletion of Inorganic Phosphate Determines the Severity of the Disturbance of Adenine Nucleotide Metabolism in the Liver and Renal Cortex of the Fructose-Loaded Rat

Evidence that the Severity of Depletion of Inorganic Phosphate Determines the Severity of the Disturbance of Adenine Nucleotide Metabolism in the Liver and Renal Cortex of the Fructose-Loaded Rat

Recovery of the Cell Cycle Inhibition inCCl4-Induced Cirrhosis by the Adenosine Derivative IFC-305

Evidence for a substrate cycle between AMP and adenosine in isolated hepatocytes.

Contact Info

Product

Resources

About