3,5-di-t-butyl-4-hydroxyanisole (DTBHA) activation of rat skeletal muscle sarcoplasmic reticulum Ca(2+)-ATPase

Biochem Pharmacol. 2001 Dec 15;62(12):1613-9. doi: 10.1016/s0006-2952(01)00794-8.

Abstract

3,5-Di-t-butyl-4-hydroxyanisole (DTBHA) increased in a concentration-dependent manner (calculated pEC(50) = 4.55 +/- 0.18 M) the oxalate-stimulated Ca(2+)-pumping rate of rat skeletal muscle sarcoplasmic reticulum (SR) vesicles. Kinetic analysis of this effect suggested that the activation of SR Ca(2+)-ATPase operated by (DTBHA) was of both mixed and non-competitive type with respect to ATP in the range of concentrations 0.1-0.5 mM and above 1 mM, respectively; furthermore, it was independent of the free Ca(2+) concentrations. This indicated that the enzyme activation took place through the acceleration of the enzyme-substrate complex breakdown. Moreover, it appeared that its target site was cyclopiazonic acid sensitive. The uncommon ability of (DTBHA) to upregulate SR Ca(2+) uptake is of interest in view of its possible use for treating pathological conditions characterised by cell Ca(2+) overload as well as genetic disorders where SR Ca(2+) homeostasis is altered.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Animals
  • Antioxidants / pharmacology
  • Biological Transport / drug effects
  • Butylated Hydroxyanisole / analogs & derivatives*
  • Butylated Hydroxyanisole / pharmacology*
  • Calcium / metabolism*
  • Calcium-Transporting ATPases / metabolism*
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • In Vitro Techniques
  • Indoles / pharmacology
  • Muscle, Skeletal / drug effects*
  • Muscle, Skeletal / enzymology
  • Rats
  • Sarcoplasmic Reticulum / drug effects*
  • Sarcoplasmic Reticulum / enzymology

Substances

  • Antioxidants
  • Indoles
  • Butylated Hydroxyanisole
  • 3,5-di-tert-butyl-4-hydroxyanisole
  • Adenosine Triphosphate
  • Calcium-Transporting ATPases
  • Calcium
  • cyclopiazonic acid