Heavy chain ferritin acts as an antiapoptotic gene that protects livers from ischemia reperfusion injury.

P. O. Berberat, M. Katori, E. Kaczmarek, D. Anselmo, C. Lassman, B. Ke, X. Shen, R. W. Busuttil, Kenichiro Yamashita, Eva Csizmadia, Shivraj Tyagi, Leo E. Otterbein, S. Brouard, E. Tobiasch, F. H. Bach, J. W. Kupiec-Weglinski, M. P. Soares

Research output: Contribution to journalArticlepeer-review

191 Scopus citations

Abstract

Heme oxygenase-1 (HO-1) is induced under a variety of pro-oxidant conditions such as those associated with ischemia-reperfusion injury (IRI) of transplanted organs. HO-1 cleaves the heme porphyrin ring releasing Fe2+, which induces the expression of the Fe2+ sequestering protein ferritin. By limiting the ability of Fe2+ to participate in the generation of free radicals through the Fenton reaction, ferritin acts as an anti-oxidant. We have previously shown that HO-1 protects transplanted organs from IRI. We have linked this protective effect with the anti-apoptotic action of HO-1. Whether the iron-binding properties of ferritin contributed to the protective effect of HO-1 was not clear. We now report that recombinant adenovirus mediated overexpression of the ferritin heavy chain (H-ferritin) gene protects rat livers from IRI and prevents hepatocellular damage upon transplantation into syngeneic recipients. The protective effect of H-ferritin is associated with the inhibition of endothelial cell and hepatocyte apoptosis in vivo. H-ferritin protects cultured endothelial cells from apoptosis induced by a variety of stimuli. These findings unveil the anti-apoptotic function of H-ferritin and suggest that H-ferritin can be used in a therapeutic manner to prevent liver IRI and thus maximize the organ donor pool used for transplantation.

Original languageEnglish (US)
Pages (from-to)1724-1726
Number of pages3
JournalThe FASEB journal : official publication of the Federation of American Societies for Experimental Biology
Volume17
Issue number12
DOIs
StatePublished - Sep 2003

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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