Inhibitory characteristics of 3,5-dibromo-1-acetoxy-4-oxo-2,5-cyclohexadien-1-acetonitrile, a semisynthetic derivative of aeroplysinin-1 from sponges (Aplysinidae), on Na+ - K+-ATPase

Boris A Gorshkov, I. A. Gorshkova, T. N. Makarieva

Research output: Contribution to journalArticle

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Abstract

3,5-Dibromo-1-acetoxy-4-oxo-2,5-cyclohexadien-1-acetonitrile (dienone A) inhibited Na+ - K+-ATPase with a half-maximal inhibition concentration (i50) equal to 2.9 × 10-6 M. Inhibition was time- and pH-dependent and complete after 20-30 min preincubation within a range of pH from 7.0 to 9.0. Kinetic evaluation of the cationic substrate activation of Na+ - K+-ATPase indicated mixed type inhibition with regard to Na+ and K+ and competitive inhibition with regard to ATP activation of the enzyme. The presence of Mg2+ caused an increased inhibition. Also, K+-p-nitrophenyl phosphatase activity was altered by dienone A and mixed type inhibition with regard to p-nitrophenyl phosphate and K+ was demonstrated. Inhibition was partially restored by repeated washing. Preincubation with sulfhydryl reagents protected the enzyme from inhibition. A significant linear correlation between reactive enzyme sulfhydryl contents [SH] and Na+ - K+-ATPase activity in the presence of varying concentrations of dienone A was observed. One of the factors causing cytotoxic activity of this compound might be its interaction with some thiol groups of the membrane-bound Na+ - K+-ATPase.

Original languageEnglish (US)
Pages (from-to)441-449
Number of pages9
JournalToxicon
Volume22
Issue number3
DOIs
StatePublished - Jan 1 1984

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Porifera
Adenosine Triphosphatases
Derivatives
Enzymes
4-Nitrophenylphosphatase
Chemical activation
Sulfhydryl Reagents
Enzyme Activation
Sulfhydryl Compounds
Washing
Adenosine Triphosphate
Membranes
Kinetics
acetonitrile
aeroplysinin I
sodium-translocating ATPase
Substrates
dienone A

ASJC Scopus subject areas

  • Toxicology

Cite this

Inhibitory characteristics of 3,5-dibromo-1-acetoxy-4-oxo-2,5-cyclohexadien-1-acetonitrile, a semisynthetic derivative of aeroplysinin-1 from sponges (Aplysinidae), on Na+ - K+-ATPase. / Gorshkov, Boris A; Gorshkova, I. A.; Makarieva, T. N.

In: Toxicon, Vol. 22, No. 3, 01.01.1984, p. 441-449.

Research output: Contribution to journalArticle

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title = "Inhibitory characteristics of 3,5-dibromo-1-acetoxy-4-oxo-2,5-cyclohexadien-1-acetonitrile, a semisynthetic derivative of aeroplysinin-1 from sponges (Aplysinidae), on Na+ - K+-ATPase",
abstract = "3,5-Dibromo-1-acetoxy-4-oxo-2,5-cyclohexadien-1-acetonitrile (dienone A) inhibited Na+ - K+-ATPase with a half-maximal inhibition concentration (i50) equal to 2.9 × 10-6 M. Inhibition was time- and pH-dependent and complete after 20-30 min preincubation within a range of pH from 7.0 to 9.0. Kinetic evaluation of the cationic substrate activation of Na+ - K+-ATPase indicated mixed type inhibition with regard to Na+ and K+ and competitive inhibition with regard to ATP activation of the enzyme. The presence of Mg2+ caused an increased inhibition. Also, K+-p-nitrophenyl phosphatase activity was altered by dienone A and mixed type inhibition with regard to p-nitrophenyl phosphate and K+ was demonstrated. Inhibition was partially restored by repeated washing. Preincubation with sulfhydryl reagents protected the enzyme from inhibition. A significant linear correlation between reactive enzyme sulfhydryl contents [SH] and Na+ - K+-ATPase activity in the presence of varying concentrations of dienone A was observed. One of the factors causing cytotoxic activity of this compound might be its interaction with some thiol groups of the membrane-bound Na+ - K+-ATPase.",
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T1 - Inhibitory characteristics of 3,5-dibromo-1-acetoxy-4-oxo-2,5-cyclohexadien-1-acetonitrile, a semisynthetic derivative of aeroplysinin-1 from sponges (Aplysinidae), on Na+ - K+-ATPase

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AU - Makarieva, T. N.

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N2 - 3,5-Dibromo-1-acetoxy-4-oxo-2,5-cyclohexadien-1-acetonitrile (dienone A) inhibited Na+ - K+-ATPase with a half-maximal inhibition concentration (i50) equal to 2.9 × 10-6 M. Inhibition was time- and pH-dependent and complete after 20-30 min preincubation within a range of pH from 7.0 to 9.0. Kinetic evaluation of the cationic substrate activation of Na+ - K+-ATPase indicated mixed type inhibition with regard to Na+ and K+ and competitive inhibition with regard to ATP activation of the enzyme. The presence of Mg2+ caused an increased inhibition. Also, K+-p-nitrophenyl phosphatase activity was altered by dienone A and mixed type inhibition with regard to p-nitrophenyl phosphate and K+ was demonstrated. Inhibition was partially restored by repeated washing. Preincubation with sulfhydryl reagents protected the enzyme from inhibition. A significant linear correlation between reactive enzyme sulfhydryl contents [SH] and Na+ - K+-ATPase activity in the presence of varying concentrations of dienone A was observed. One of the factors causing cytotoxic activity of this compound might be its interaction with some thiol groups of the membrane-bound Na+ - K+-ATPase.

AB - 3,5-Dibromo-1-acetoxy-4-oxo-2,5-cyclohexadien-1-acetonitrile (dienone A) inhibited Na+ - K+-ATPase with a half-maximal inhibition concentration (i50) equal to 2.9 × 10-6 M. Inhibition was time- and pH-dependent and complete after 20-30 min preincubation within a range of pH from 7.0 to 9.0. Kinetic evaluation of the cationic substrate activation of Na+ - K+-ATPase indicated mixed type inhibition with regard to Na+ and K+ and competitive inhibition with regard to ATP activation of the enzyme. The presence of Mg2+ caused an increased inhibition. Also, K+-p-nitrophenyl phosphatase activity was altered by dienone A and mixed type inhibition with regard to p-nitrophenyl phosphate and K+ was demonstrated. Inhibition was partially restored by repeated washing. Preincubation with sulfhydryl reagents protected the enzyme from inhibition. A significant linear correlation between reactive enzyme sulfhydryl contents [SH] and Na+ - K+-ATPase activity in the presence of varying concentrations of dienone A was observed. One of the factors causing cytotoxic activity of this compound might be its interaction with some thiol groups of the membrane-bound Na+ - K+-ATPase.

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