Reversible inhibition of caspase-3 activity by iron(III): potential role in physiological control of apoptosis.
Desferoxamine is known to induce apoptosis in cancer cells, but the mechanisms are still not fully understood. We have shown that iron(III) is a potent caspase-3 inhibitor, and the inhibition is reversible by the iron chelating agent desferoxamine. Also, protein disulfide isomerase (PDI) is capable of activating caspase-3 inhibited by iron(III), likely by formation of iron-sulfur complex through its active site thiols. Data presented here suggests that iron(III) could be a potential inhibitor of apoptosis in vivo, by caspase-3-dependent inhibition with a possibility of recovery through PDI overexpression.
Sliskovic
Inga
I
Department of Chemistry and Biochemistry, University of Windsor, 401 Sunset Avenue, Windsor, Ont., Canada N9B 3P4.
Mutus
Bulent
B
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D053148:Caspase 3; D020169:Caspases / Q000737:chemistry* / Q000378:metabolism; D003676:Deferoxamine / Q000737:chemistry / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000737:chemistry*; D005290:Ferric Compounds / Q000737:chemistry*; D006801:Humans; D009369:Neoplasms / Q000201:enzymology; D019704:Protein Disulfide-Isomerases / Q000737:chemistry* / Q000378:metabolism; D017262:Siderophores / Q000737:chemistry / Q000494:pharmacology
D004791:Enzyme Inhibitors; D005290:Ferric Compounds; D017262:Siderophores; C024823:ferric sulfate; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D019704:Protein Disulfide-Isomerases; D003676:Deferoxamine