The organotellurium compound ammonium trichloro(dioxoethylene-o,o′) tellurate reacts with homocysteine to form homocystine and decreases homocysteine levels in hyperhomocysteinemic mice

Eitan Okun, Yahav Dikshtein, Alon Carmely, Hagar Saida, Gabi Frei, Ben Ami Sela, Lydia Varshavsky, Asher Ofir, Esthy Levy, Michael Albeck, Benjamin Sredni*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)3159-3170
Number of pages12
JournalFEBS Journal
Volume274
Issue number12
DOIs
StatePublished - Jun 2007
Externally publishedYes

Keywords

  • AS101
  • Homocysteine
  • Hyperhomocysteinemia
  • Organotellurium
  • Tellurium

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