File Download

There are no files associated with this item.

  Links for fulltext
     (May Require Subscription)
Supplementary

Article: Haem control in experimental porphyria. The effect of haemin on the induction of δ-aminolaevulinate synthase in isolated chick-embryo liver cells

TitleHaem control in experimental porphyria. The effect of haemin on the induction of δ-aminolaevulinate synthase in isolated chick-embryo liver cells
Authors
Issue Date1980
PublisherPortland Press Ltd. The Journal's web site is located at http://www.biochemj.org
Citation
Biochemical Journal, 1980, v. 188 n. 3, p. 781-788 How to Cite?
Abstract2-Allyl-2-isopropylacetamide-mediated induction of hepatic porphyria was studied in isolated chick-embryo liver cells. Increased δ-aminolaevulinate synthase activity occurred within 1 h of induction and continued to increase for 8 h. Protoporphyrins synthesized during this time accumulated to a concentration 1-fold greater than that in the control. Removal of 2-allyl-2-isopropylacetamide from the cells by washing at 3 h immediately inhibited further increases in δ-aminolaevulinate synthase synthesis. However substitution of 2-allyl-2-isopropylacetamide at 3 h by deferoxamine methane-sulphonate, an inhibitor of haem synthesis, allowed continued δ-aminolaevulinate synthase induction at an unaltered rate, even though this agent did not, by itself, induce enzyme synthesis. Exogenously added haemin was shown completely to inhibit 2-allyl-2-isopropylacetamide-mediated δ-aminolaevulinate synthase induction at concentrations as low as 20 nM, a value that is less than the reported physiological one. The duration of inhibition was dependent on the concentration of added haemin and was followed by period of δ-aminolaevulinate synthase synthesis at a rate similar to that of the control. These data are consistent with the hypothesis that δ-aminolaevulinate synthase synthesis is regulated by the concentration of intracellular haem and that induction is initiated by 2-allyl-2-isopropylacetamide-mediated destruction of haem. Induction of δ-aminolaevulinate synthase was shown to be dependent on both RNA and protein synthesis, and a study of the comparative effects of cordycepin, cycloheximide and haem has shown that, at haemin concentrations up to 50 nM, the inhibition of δ-aminolaevulinate synthase synthesis followed kinetics similar to the effect of cordycepin, with no synergism between cordycepin and 50nM-haemin. However, at a haemin concentration of 2 μM, the inhibition of δ-aminolaevulinate synthase synthesis followed similar kinetics to the effect of cycloheximide. These data demonstrate the control of δ-aminolaevulinate synthase synthesis by low concentrations of haemin and suggests that the primary effect of haemin is at the level of transcription.
Persistent Identifierhttp://hdl.handle.net/10722/147729
ISSN
2015 Impact Factor: 3.562
2015 SCImago Journal Rankings: 2.582
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorSrivastava, Gen_US
dc.contributor.authorBrooker, JDen_US
dc.contributor.authorMay, BKen_US
dc.contributor.authorElliott, WHen_US
dc.date.accessioned2012-05-29T06:08:56Z-
dc.date.available2012-05-29T06:08:56Z-
dc.date.issued1980en_US
dc.identifier.citationBiochemical Journal, 1980, v. 188 n. 3, p. 781-788en_US
dc.identifier.issn0264-6021en_US
dc.identifier.urihttp://hdl.handle.net/10722/147729-
dc.description.abstract2-Allyl-2-isopropylacetamide-mediated induction of hepatic porphyria was studied in isolated chick-embryo liver cells. Increased δ-aminolaevulinate synthase activity occurred within 1 h of induction and continued to increase for 8 h. Protoporphyrins synthesized during this time accumulated to a concentration 1-fold greater than that in the control. Removal of 2-allyl-2-isopropylacetamide from the cells by washing at 3 h immediately inhibited further increases in δ-aminolaevulinate synthase synthesis. However substitution of 2-allyl-2-isopropylacetamide at 3 h by deferoxamine methane-sulphonate, an inhibitor of haem synthesis, allowed continued δ-aminolaevulinate synthase induction at an unaltered rate, even though this agent did not, by itself, induce enzyme synthesis. Exogenously added haemin was shown completely to inhibit 2-allyl-2-isopropylacetamide-mediated δ-aminolaevulinate synthase induction at concentrations as low as 20 nM, a value that is less than the reported physiological one. The duration of inhibition was dependent on the concentration of added haemin and was followed by period of δ-aminolaevulinate synthase synthesis at a rate similar to that of the control. These data are consistent with the hypothesis that δ-aminolaevulinate synthase synthesis is regulated by the concentration of intracellular haem and that induction is initiated by 2-allyl-2-isopropylacetamide-mediated destruction of haem. Induction of δ-aminolaevulinate synthase was shown to be dependent on both RNA and protein synthesis, and a study of the comparative effects of cordycepin, cycloheximide and haem has shown that, at haemin concentrations up to 50 nM, the inhibition of δ-aminolaevulinate synthase synthesis followed kinetics similar to the effect of cordycepin, with no synergism between cordycepin and 50nM-haemin. However, at a haemin concentration of 2 μM, the inhibition of δ-aminolaevulinate synthase synthesis followed similar kinetics to the effect of cycloheximide. These data demonstrate the control of δ-aminolaevulinate synthase synthesis by low concentrations of haemin and suggests that the primary effect of haemin is at the level of transcription.en_US
dc.languageengen_US
dc.publisherPortland Press Ltd. The Journal's web site is located at http://www.biochemj.orgen_US
dc.relation.ispartofBiochemical Journalen_US
dc.subject.mesh5-Aminolevulinate Synthetase - Antagonists & Inhibitors - Biosynthesisen_US
dc.subject.meshAllylisopropylacetamide - Pharmacologyen_US
dc.subject.meshAnimalsen_US
dc.subject.meshChick Embryoen_US
dc.subject.meshEnzyme Induction - Drug Effectsen_US
dc.subject.meshHeme - Analogs & Derivatives - Metabolismen_US
dc.subject.meshHemin - Pharmacologyen_US
dc.subject.meshLiver - Drug Effects - Embryology - Enzymologyen_US
dc.subject.meshPorphyrias - Metabolismen_US
dc.titleHaem control in experimental porphyria. The effect of haemin on the induction of δ-aminolaevulinate synthase in isolated chick-embryo liver cellsen_US
dc.typeArticleen_US
dc.identifier.emailSrivastava, G:gopesh@pathology.hku.hken_US
dc.identifier.authoritySrivastava, G=rp00365en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.pmid7470035-
dc.identifier.scopuseid_2-s2.0-0019307740en_US
dc.identifier.volume188en_US
dc.identifier.issue3en_US
dc.identifier.spage781en_US
dc.identifier.epage788en_US
dc.identifier.isiWOS:A1980KB35000026-
dc.publisher.placeUnited Kingdomen_US

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats