The discovery of a rapidly metabolized polymeric tetraphosphate derivative of adenosine in perfused rat heart

Mowbray, John; Hutchinson, Winston L.; Tibbs, Gareth R.; Morris, Peter G.

doi:10.1042/bj2230627

Cited by 17 publications

(34 citation statements)

References 26 publications

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“…Purinogen has been suggested to play an important role as an energy reserve in the rat heart [3]. To eventually prove the presence of purinogen in endothelial cells could explain their extraordinary ability to survive under conditions of exogenous substrate deprivation.…”

Section: Discussionmentioning

confidence: 99%

“…(4) The evidence supporting the presence of purinogen was originally based on adenosine-labelling experiments of the perfused rat heart [3]. It is known that endothelial cells in the heart are quantitatively primarily responsible for adenosine uptake [13].…”

Section: Discussionmentioning

confidence: 99%

“…Labelling of rat hearts with ["%C]adenosine revealed the existence of a rapidly labelled trichloroacetic acid-insoluble nucleotide pool [3]. It has been reported that, quantitatively, this pool corresponds to approx.…”

Section: Introductionmentioning

confidence: 99%

“…No substantial energy reserve in the form of phosphocreatine or glycogen could be detected [2]. Most likely, survival of cells, as well as purine release, during substrate deprivation is supported by certain endogenous substrates which remain elusive at present.Labelling of rat hearts with ["%C]adenosine revealed the existence of a rapidly labelled trichloroacetic acid-insoluble nucleotide pool [3]. It has been reported that, quantitatively, this pool corresponds to approx.…”

mentioning

confidence: 99%

“…25-55 % of the total acid-soluble adenine nucleotide pool [4,5]. Preparative biochemistry combined with diverse analytical methods showed that a phosphate derivative of adenosine is a main building block of this polymeric adenine nucleotide, named purinogen [3,6]. It has been proposed that purinogen might play an important role as an energy reserve in the heart and also in other tissues such as liver and kidney [5][6][7][8].…”

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confidence: 99%

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Purinogen is not an endogenous substrate used in endothelial cells during substrate deprivation

Čulić

Decking

Bergschneider

et al. 1999

Biochemical Journal

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Porcine aortic endothelial cells (PAEC) are known to be metabolically robust. They are capable of surviving extended periods of complete lack of exogenous substrate, and purine release has been shown to be significantly up-regulated. The endogenous substrates used during substrate deprivation, as well as the sources responsible for the increased purine release, have not been completely identified. We tested the possibility that a phosphoglyceroyl-ATP-containing polymer, purinogen, might support PAEC hibernation induced by lack of exogenous substrate. This involved isolation of the acid-insoluble fraction of PAEC, which was presumed to contain purinogen, and analysis by HPLC and $"P NMR. No evidence supporting the presence of triphosphate-containing compounds (purinogen) was found. Similar results were obtained in the rat heart. The majority of the products in the acid-insoluble, alkaline-treated fraction were INTRODUCTIONIn a previous study we showed that porcine aortic endothelial cells (PAEC) can survive at least 2 h of perfusion with a substratefree medium [1]. Although their intracellular adenine nucleotide content, as well as energy turnover, was drastically decreased during this phase, they were capable of fully recovering upon reperfusion with a glucose-containing medium [1,2]. Furthermore, purine nucleoside and nucleobase release of PAEC, under conditions of exogenous substrate lack, was significantly upregulated. The increased de no o synthesis of purines, which contributed to the increase in purine release, did not fully explain these findings. No substantial energy reserve in the form of phosphocreatine or glycogen could be detected [2]. Most likely, survival of cells, as well as purine release, during substrate deprivation is supported by certain endogenous substrates which remain elusive at present.Labelling of rat hearts with ["%C]adenosine revealed the existence of a rapidly labelled trichloroacetic acid-insoluble nucleotide pool [3]. It has been reported that, quantitatively, this pool corresponds to approx. 25-55 % of the total acid-soluble adenine nucleotide pool [4,5]. Preparative biochemistry combined with diverse analytical methods showed that a phosphate derivative of adenosine is a main building block of this polymeric adenine nucleotide, named purinogen [3,6]. It has been proposed that purinogen might play an important role as an energy reserve in the heart and also in other tissues such as liver and kidney [5][6][7][8].In view of these findings we explored whether purinogen is present in endothelial cells and whether its presence could explain the remarkable ability of this cell type to survive extended Abbreviations used : PAEC, porcine aortic endothelial cells ; FID, free induction decay. 1 To whom correspondence should be addressed (e-mail ognjen!herzkreis.uni-duesseldorf.de).identified as RNA degradation products (2h-and 3h-nucleoside monophosphates). A ["%C]adenosine labelling experiment showed that incorporation of adenosine into the acid-insoluble fraction was almost completely pr...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Purinogen is not an endogenous substrate used in endothelial cells during substrate deprivation

Čulić

Decking

Bergschneider

et al. 1999

Biochemical Journal

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The Control of Cardiac Adenine Nucleotides: The Discovery and Potential Function of High-Energy Oligomeric Derivatives of ATP

Mowbray¹

1991

Developments in Cardiovascular Medicine

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Studies of adenosine incorporation in Langendorff rat heart and rat heart mitochondria

et al. 1987

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The acid-insoluble product isolated from well-oxygenated Langendorff rat heart after perfusion with [14C]adenosine was purified by phenol extraction and subjected to specific phosphorolysis by pure polynucleotide phosphorylase. TLC analysis of the reaction mixture showed that ADP was the only radioactive product, proving that the original substance was a polyribonucleotide. Studies of the time course of labelling and of the distribution of the acid-insoluble product between the mitochondrial and nuclear fractions showed that both are labelled even after 1 min at 25 degrees C, but at short times and low temperature more radioactivity is found in the mitochondria. The kinetics of adenosine incorporation resemble those expected for the labelling of hnRNA and mRNA. Isolated, respiring mitochondria incorporate adenosine and adenine nucleotides into acid insoluble form by a process dependent on oxidative phosphorylation and the adenine nucleotide translocase that is specific for adenine derivatives. The results are discussed in terms of the hypothesis that the polyribonucleotide might be a storage form of adenine nucleotides: it is concluded that the bulk of the labelled product is unlikely to play a major role in energy metabolism.

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The discovery of a rapidly metabolized polymeric tetraphosphate derivative of adenosine in perfused rat heart

Cited by 17 publications

References 26 publications

Purinogen is not an endogenous substrate used in endothelial cells during substrate deprivation

Purinogen is not an endogenous substrate used in endothelial cells during substrate deprivation

The Control of Cardiac Adenine Nucleotides: The Discovery and Potential Function of High-Energy Oligomeric Derivatives of ATP

Studies of adenosine incorporation in Langendorff rat heart and rat heart mitochondria

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