Antioxidant defense against anthracycline cardiotoxicity by metallothionein

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Anthracycline cardiotoxicity is related to oxidative stress generated from the metabolism of anthracyclines in the heart. Studies using transgenic mice with high levels of antioxidants such as catalase or metallothionein (MT) specifically in the heart have demonstrated that elevation of cardiac antioxidant defense leads to intervention of anthracycline cardiotoxicity. MT protection against anthracycline-induced cardiac toxicity is related to its anti-apoptotic effect by inhibiting both p38-MAPK-mediated and mitochondrial cytochrome c-release-mediated apoptotic signaling. The anti-apoptotic effect of MT is closely related to its antioxidant action, which involves regulation of zinc homeostasis by the MT redox cycle. MT interferes with oxidant-mediated detrimental process through at least in part zinc release and zinc transfers directly from MT to acceptor proteins. In addition, MT posttranslationally modulates critical proteins involved in mitochondrial respiration and energy metabolism. All of these processes constitute the mechanisms by which MT protects from anthracycline cardiotoxicity.

Original languageEnglish (US)
Pages (from-to)95-100
Number of pages6
JournalCardiovascular Toxicology
Volume7
Issue number2
DOIs
StatePublished - Jun 1 2007
Externally publishedYes

Fingerprint

Metallothionein
Anthracyclines
Antioxidants
Zinc
p38 Mitogen-Activated Protein Kinases
Oxidative stress
Cytochromes c
Cardiotoxicity
Oxidants
Catalase
Energy Metabolism
Transgenic Mice
Oxidation-Reduction
Metabolism
Respiration
Proteins
Oxidative Stress
Homeostasis
Toxicity

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Toxicology
  • Cardiology and Cardiovascular Medicine

Cite this

Antioxidant defense against anthracycline cardiotoxicity by metallothionein. / Kang, Yujian.

In: Cardiovascular Toxicology, Vol. 7, No. 2, 01.06.2007, p. 95-100.

Research output: Contribution to journalArticle

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