-transparent.png){kind=logo}
Hydrogen peroxide (H2O2) at millimolar concentrations induces Ca2+ release from actively loaded sarcoplasmic reticulum vesicles and induces biphasic [3H]ryanodine binding behavior. High affinity [3H]ryanodine binding is enhanced at concentrations from 100 microM to 10 mM (3-4 fold). At H2O2 concentrations greater than 10 mM, equilibrium binding is inhibited. H2O2 decreased the kd for [3H]ryanodine binding by increasing its association rate, while having no effect on the rate of dissociation of [3H]ryanodine from its receptor. H2O2 (1 mM) also reduced the EC50 for Ca2+ activation from 632 nM to 335 nM. These effects were completely abolished in the presence of catalase, ruthenium red, and/or Mg2+ (Mm). H2O2-stimulated [3H]ryanodine binding is not further enhanced by either doxorubicin or caffeine. The direct interaction between H2O2 and the Ca2+ release mechanism was further demonstrated in single-channel reconstitution experiments. Peroxide, at submillimolar concentrations, activated the Ca2+ release channel following fusion of a sarcoplasmic reticulum vesicle to a bilayer lipid membrane. At millimolar concentrations of peroxide, Ca2+ channel activity was inhibited. Peroxide stimulation of Ca2+ channel activity was reversed by the thiol reducing agent dithiothreitol. Paralleling peroxide induced activation of ryanodine binding, Ca2+ transport, and single Ca2+ channel activity, it was observed that the ryanodine receptor formed large disulfide-linked protein complexes that dissociated upon addition of dithiothreitol.
T G Favero, and
A C Zable, and
J J Abramson
August 1996,
Journal of applied physiology (Bethesda, Md. : 1985),
T G Favero, and
A C Zable, and
J J Abramson
February 1992,
Archives of biochemistry and biophysics,
T G Favero, and
A C Zable, and
J J Abramson
December 2002,
Proceedings of the National Academy of Sciences of the United States of America,
T G Favero, and
A C Zable, and
J J Abramson
December 1992,
Molecular pharmacology,
T G Favero, and
A C Zable, and
J J Abramson
September 1985,
The Journal of biological chemistry,
T G Favero, and
A C Zable, and
J J Abramson
January 1988,
Methods in enzymology,
T G Favero, and
A C Zable, and
J J Abramson
July 1985,
FEBS letters,
T G Favero, and
A C Zable, and
J J Abramson
March 1994,
Biochemistry and molecular biology international,
T G Favero, and
A C Zable, and
J J Abramson
October 1984,
Physiological reviews,
T G Favero, and
A C Zable, and
J J Abramson
February 1997,
The American journal of physiology,
