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Roles of ferritin and iron in ischemic preconditioning of the heart

  • Eduard Berenshtein
  • Boris Vaisman
  • Chaya Goldberg-Langerman
  • Nahum Kitrossky
  • Abraham M. Konijn
  • Mordechai Chevion
Part of the Developments in Molecular and Cellular Biochemistry book series (DMCB, volume 37)

Abstract

Iron and copper play major roles in biological systems, catalyzing free radical production and consequently causing damage. The relatively high levels of these metals, which are mobilized into the coronary flow following prolonged ischemia, have been incriminated as key players in reperfusion injury to the heart. In the present communication we investigated other roles of iron — providing protection to the ischemic heart via preconditioning (PC).

PC was accomplished by subjecting isolated rat hearts to three episodes of2 min ischemia separated by 3 min ofreperfusion. Prolonged ischemia followed the PC phase. PC hearts (group I) were compared to hearts subjected to normal perfusion (group II, no ischemia) and to ischemia without PC (group III). Group I showed a marked improvement in the recovery ofhemodynamic function vs. group III. Biochemical parameters further substantiated the PC protection provided to group I against prolonged ischemia. Correspondingly, group I presented markedly lower re-distribution and mobilization of iron and copper into the coronary flow, following prolonged ischemia, as evinced from the decrease in total levels, and in the ‘free’ fraction ofiron and copper.

During the PC phase no loss of cardiac function was observed. A small wave of re-distribution and mobilization of iron (typically less than 4-8% ofthe value of35 min ischemia) was recorded. The cellular content of ferritin (Ft) measured in the heart was significantly higher in group I than in group III (0.90 and 0.54 /lg/mg, respectively). Also, iron-saturation ofFt was significantly lower for PC hearts, compared to both groups II and III (0.22 vs. 0.32 and 0.31 /lg/mg, for 35 min ischemia, respectively). These findings are in accord with the proposal that intracellular re-distribution and mobilization of small levels of iron, during PC, cause rapid accumulation of ferritin - the major iron-storage protein.

It is proposed that iron playa dual role: (i) It serves as a signaling pathway for the accumulation of Ft following the PC phase. This iron is not involved in cardiac injury, but rather prepares the heart against future high levels of ‘free’ iron, thus reducing the degree of myocardial damage after prolonged ischemia. (ii) High levels of iron (and copper) are mobilized following prolonged ischemia and cause tissue damage. (Mol Cell Biochem 234/235: 283-292, 2002)

Key words

heart protection preconditioning ischemia iron ferritin reperfusion injury isolated rat heart free radicals 

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Copyright information

© Springer Science+Business Media New York 2002

Authors and Affiliations

  • Eduard Berenshtein
    • 1
  • Boris Vaisman
    • 2
  • Chaya Goldberg-Langerman
    • 1
  • Nahum Kitrossky
    • 1
  • Abraham M. Konijn
    • 2
  • Mordechai Chevion
    • 1
  1. 1.Department of Cellular Biochemistry and Human GeneticsJerusalemIsrael
  2. 2.Department of Human Nutrition and MetabolismThe Hebrew University-Hadassah Schools of Medicine and Dental MedicineJerusalemIsrael

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