Conclusions

Thus all the agents investigated (HgCl₂, CdCl₂ and glycerol action) cause the accumulation of heme in PMch, induction of ALAS and HO and decrease of CytP450 content in liver. But only HgCl₂ and glycerol cause GSH level decrease and accumulation of heme in mitochondria accompanied by increase of TDO heme saturation. Membrane stabilisation by tocopherol or prevention of early ALAS induction by cycloheximide prevent both Mch heme accumulation and increase of TDO%. Taking into account the presence of numerous heme-binding sites within cell including cytosol proteins (guanylate cyclase, NO synthase) and nuclear sites [1,2] heme molecule (first of all free heme) may be widely involved in signaling mechanisms under stress agents action. Our work provides some evidence on participation of newly synthesized heme in free heme pool formation under action of agents causing membrane damage and changes in redox state.

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Acknowledgments

We particularly thank Professor Jacques E. DUMONT and Organizing Committee for granting the travel to Special FEBS 2003 Meeting.