Met-
myoglobin [Fe(III)] was found to induce
myosin cross-linking in the presence of H2O2 [Bhoite-Solomon, V. & Shaklai, N. (1992) Biochem. Int. 26, 181-189]. To assess the relevance of these findings to cellular pathology, peroxidation of
myosin was performed with physiological divalent
iron [Fe(II)] myoglobins in the oxy and deoxy forms. Both
myoglobin forms were capable of mediating cross-linking of
myosin.
Deoxymyoglobin reactivity was similar to that of met-
myoglobin, but the reactivity of
oxymyoglobin was retarded compared to
deoxymyoglobin. Cross-linking of
myosin occurred under a low flow rate of H2O2 (3 microM/min) and in the presence of excess
oxymyoglobin over H2O2, known to diminish the steady state of the
myoglobin active
heme [ferryl, Fe(IV)]state. The
adenosinetriphosphatase activity of
myosin was reduced to about half due to cross-linking. Addition of
myoglobin/H2O2 to high
myosin concentrations (> = 20 microM) turned the solutions into
gels, a phenomenon explained by the further formation of intermolecular super cross-links of soluble
myosin. Thus, at cellular ionic strength in which
myosin is insoluble, cross-linking of
myosin could still be triggered by
myoglobin and H2O2. Based on these data, it is suggested that
myoglobin-induced cross-linking of
myosin and the consequent loss of
adenosinetriphosphatase activity may be involved in muscle malfunction under
hypoxia when cellular peroxidants increase and the
deoxymyoglobin form prevails.