Name: RENATA ANDRADE ÁVILA
Publication date: 30/05/2016
Advisor:
Name |
Role |
|---|---|
| LEONARDO DOS SANTOS | Advisor * |
Examining board:
| Name |
Role |
|---|---|
| ANDRÉ SOARES LEOPOLDO | External Examiner * |
| DANILO SALES BOCALINI | External Examiner * |
| LEONARDO DOS SANTOS | Advisor * |
| MARCELO PERIM BALDO | Internal Examiner * |
Summary: Iron overload can damage several organs including the cardiovascular system, and is a leading cause of poisoning deaths in children. The purpose of this study was to examine whether acute ferrous iron (Fe2+) can differently interfere on the myocardial mechanics, investigating the ROS-mediated effects on the excitation-contraction coupling. METHODS: Intact membrane and Triton-skinned rat papillary muscles were used. The activity of myosin ATPase was measured. Protocols with intact papillary muscles were repeated in the presence of antioxidants CAT, DMSO and TEMPOL, and ROS were measured. RESULTS: Developed force was depressed in a concentration- and time-dependent manner by Fe2+, and at 100 and 1000microM, Fe2+ reduced the response to extracellular Ca2+ increase, which was partially reversed by CAT and DMSO, but not TEMPOL. Accordingly, the OH measurement by HPF dye indicated higher levels after incubation with Fe2+, WHEREas O2 - as measured by the DHE dye was unchanged.The myosin ATPase activity was decreased by 100 and 1000microM Fe2+. Contractions dependent on the sarcolemal Ca2+ influx were impaired only by1000 microM Fe2+, and antioxidants had no effect. In skinned fibers, Fe2+ caused significant reduction in the pCa-force relationship, and pCa50 value was left-shifted by approximately 0.55. CONCLUSION: Iron overload can acutely generate ROS and impair myocardial contractility by reducing the capacity to generate force associated to reduced myosin ATPase activity and miofibrilar Ca2+ sensitivity. These effects are, at least in part, mediated by local production of OH and H2O2. Nevertheless, in a such high concentration as 1000 microM, Fe2+ appears to depress force also by reducing Ca2+ influx, which is not dependent of oxidative stress but probably due to Fe2+compete with Ca2+by its channels.
