title: The organotellurium compound ammonium trichloro(dioxoethylene-o,o')tellurate reacts with homocysteine to form homocystine and decreases homocysteine levels in hyperhomocysteinemic mice.
abstract: Ammonium trichloro(dioxoethylene-o,o')tellurate (AS101) is an organotellurium compound with pleiotropic functions that has been associated with antitumoral, immunomodulatory and antineurodegenerative activities. Tellurium compounds with a +4 oxidation state, such as AS101, react uniquely with thiols, forming disulfide molecules. In light of this, we tested whether AS101 can react with the amino acid homocysteine both in vitro and in vivo. AS101 conferred protection against homocysteine-induced apoptosis of HL-60 cells. The protective mechanism of AS101 against homocysteine toxicity was directly mediated by its chemical reactivity, whereby AS101 reacted with homocysteine to form homocystine, the less toxic disulfide form of homocysteine. Moreover, AS101 was shown here to reduce the levels of total homocysteine in an in vivo model of hyperhomocysteinemia. As a result, AS101 also prevented sperm cells from undergoing homocysteine-induced DNA fragmentation. Taken together, our results suggest that the organotellurium compound AS101 may be of clinical value in reducing total circulatory homocysteine levels.
authors.affiliation: CAIR Institute, The Safdié AIDS and Immunology Research Center, Bar-Ilan University, Ramat-Gan, Israel.
authors.forename: Eitan
authors.initials: E
authors.lastname: Okun
authors.forename: Yahav
authors.initials: Y
authors.lastname: Dikshtein
authors.forename: Alon
authors.initials: A
authors.lastname: Carmely
authors.forename: Hagar
authors.initials: H
authors.lastname: Saida
authors.forename: Gabi
authors.initials: G
authors.lastname: Frei
authors.forename: Ben-Ami
authors.initials: BA
authors.lastname: Sela
authors.forename: Lydia
authors.initials: L
authors.lastname: Varshavsky
authors.forename: Asher
authors.initials: A
authors.lastname: Ofir
authors.forename: Esthy
authors.initials: E
authors.lastname: Levy
authors.forename: Michael
authors.initials: M
authors.lastname: Albeck
authors.forename: Benjamin
authors.initials: B
authors.lastname: Sredni
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053938:DNA Fragmentation / Q000187:drug effects; D005030:Ethylenes / Q000494:pharmacology* / Q000627:therapeutic use; D018922:HL-60 Cells; D006710:Homocysteine / Q000378:metabolism*; D006711:Homocystine / Q000378:metabolism*; D006801:Humans; D020138:Hyperhomocysteinemia / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D013094:Spermatozoa / Q000473:pathology
chemical_list: D005030:Ethylenes; D006710:Homocysteine; D006711:Homocystine; C054105:ammonium trichloro(dioxoethylene-O,O'-)tellurate