Contents

πŸ“’ Lebrecht 2003

Time-dependent and tissue-specific accumulation of mtDNA and respiratory chain defects in chronic doxorubicin cardiomyopathy1

Sciwheel

Introductions

  • The mechanism for the delayed onset and the molecular basis of the β€œdose memory”: mtDNA damage, gene expression https://www.ahajournals.org/cms/attachment/d88b8423-6985-4b9a-ab9d-0859a0169b39/31ff1.jpg

Methods

Animals

https://www.ahajournals.org/cms/attachment/cee1d8cf-5a68-40ef-94d3-6eff6c59477b/31ff2.jpg

  • Male Wistar rats with control and various DOX treatment regimes

Enzyme Activity

  • cytochrome c oxidase (COX)
  • succinate dehydrogenase (SDH): entirely encoded by nuclear DNA
  • citrate synthase (CS): entirely encoded by nuclear DNA

mtDNA

  • amount
  • deletions

superoxide

  • dihydroethidium

Results

https://www.ahajournals.org/cms/attachment/e62fc5d9-ea99-4361-ac99-c31719e5e535/31ff3.jpg https://user-images.githubusercontent.com/40054455/86700689-e5dc8e00-c043-11ea-90cf-a124b8d9fd53.png https://user-images.githubusercontent.com/40054455/86700698-e7a65180-c043-11ea-8849-ab32cf5e5442.png https://www.ahajournals.org/cms/attachment/4ec93b7f-963b-4aa8-b841-d4941a07c21e/31ff5.jpg

Discussion

  • Both treatment dosing and timing are important
  • Doxorubicin accumulates in heart in high concentrations (cardiolipin) => cardiac tissue the predominant target of doxorubicin toxicity

References


  1. Lebrecht D, Setzer B, Ketelsen U-P, Haberstroh J, Walker UA. Time-dependent and tissue-specific accumulation of mtDNA and respiratory chain defects in chronic doxorubicin cardiomyopathy. Circulation 2003;108(19):2423-2429. doi:10.1161/01.CIR.0000093196.59829.DF. ↩︎