Doxorubicin interacts directly with skinned single skeletal muscle fibres.
The effect of doxorubicin, a highly effective anticancer agent, on the contractile apparatus of skinned single muscle fibres was tested in a concentration of 1 microM. Sarcomere length was set and held at 2 microns. Doxorubicin induced an increase in tension dependent on the Ca2+ concentration and time of incubation. The rise was up to 25% at [Ca2+] 40 microM. A parallel, small but significant shift of the calcium sensitivity curve, the relation between normalized tension and the negative logarithm of [Ca2+], the pCa, was observed. The results of this study suggest a direct interaction of doxorubicin with the actin myosin structure, possibly by an effect on myosin-ATP activity.
De Beer
E L
EL
Department of Medical Physiology and Sports Medicine, JJRC, Utrecht, Netherlands.
Finkle
H
H
Voest
E E
EE
Van Heijst
B G
BG
Schiereck
P
P
D000818:Animals; D002118:Calcium / Q000378:metabolism; D003497:Cyclic N-Oxides / Q000494:pharmacology; D004317:Doxorubicin / Q000494:pharmacology*; D005609:Free Radicals; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D009132:Muscles / Q000187:drug effects*; D011817:Rabbits
D003497:Cyclic N-Oxides; D005609:Free Radicals; D004317:Doxorubicin; D002118:Calcium; C003959:TEMPO