Photosensitization of intact heart mitochondria by the phthalocyanine Pc 4: Correlation of structural and functional deficits with cytochrome c release

Free Radic Biol Med. 2010 Sep 1;49(5):726-32. doi: 10.1016/j.freeradbiomed.2010.05.013. Epub 2010 May 25.

Abstract

Singlet oxygen is produced by the absorption of red light by the phthalocyanine dye Pc 4, followed by energy transfer to dissolved triplet oxygen. Mitochondria preincubated with Pc 4 were illuminated by red light and the damage to mitochondrial structure and function by the generated singlet oxygen was studied. At early illumination times (3-5 min of red light exposure), State 3 respiration was inhibited (50%), whereas State 4 activity increased, resulting in effectively complete uncoupling. Individual complex activities were measured and only complex IV activity was significantly reduced and exhibited a dose response, whereas the activities of electron transport complexes I, II, and III were not significantly affected. Cytochrome c release was an increasing function of irradiation time, with 30% being released after 5 min of illumination. Mitochondrial expansion along with changes in the structure of the cristae were observed by transmission electron microscopy after 5 min of irradiation, with an increase in large vacuoles and membrane rupture occurring after more extensive exposures.

Publication types

  • Evaluation Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cytochromes c / metabolism*
  • In Vitro Techniques
  • Indoles / pharmacology*
  • Light
  • Male
  • Mitochondria, Heart / drug effects*
  • Mitochondria, Heart / metabolism
  • Mitochondria, Heart / radiation effects*
  • Mitochondria, Heart / ultrastructure
  • Oxidative Phosphorylation / drug effects
  • Oxidative Phosphorylation / radiation effects
  • Photosensitizing Agents / pharmacology*
  • Rats
  • Rats, Inbred F344
  • Reactive Oxygen Species / metabolism

Substances

  • Indoles
  • Photosensitizing Agents
  • Reactive Oxygen Species
  • phthalocyanine Pc 4
  • Cytochromes c