A digitized-fluorescence-imaging study of mitochondrial Ca2+ increase by doxorubicin in cardiac myocytes.
The objective of the present study was to investigate the role of mitochondrial Ca2+ in doxorubicin-induced cell injury. The effect of doxorubicin on cultured cells was investigated by digitized fluorescence imaging. The Ca2+ sensitive fluorescent dye fura-2 was used to estimate cytosolic, mitochondrial and total cellular Ca2+. Rhodamine 123 was used to estimate the mitochondrial membrane potential, and cellular ATP was determined by h.p.l.c. The data showed that doxorubicin induced greater-than-2-fold increases in mitochondrial Ca2+ before changes in cytosolic Ca2+ could be detected. An increase in mitochondrial Ca2+ paralleled the observed dissipation in mitochondrial membrane potential. Cellular ATP levels appeared to decrease as a result of mitochondrial dysfunction, which in turn produced greater-than-2-fold increases in cytosolic Ca2+. The data suggest that doxorubicin-induced alterations in mitochondrial Ca2+ homoeostasis are associated with a dissipation in energy conservation, which may result in cell injury.
Chacon
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E
Division of Pharmacology and Toxicology, College of Pharmacy, University of Texas, Austin.
Ulrich
R
R
Acosta
D
D
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D004317:Doxorubicin / Q000494:pharmacology*; D004734:Energy Metabolism; D005456:Fluorescent Dyes; D016257:Fura-2; D006706:Homeostasis; D007091:Image Processing, Computer-Assisted; D008564:Membrane Potentials / Q000187:drug effects; D008856:Microscopy, Fluorescence; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D020112:Rhodamine 123; D012235:Rhodamines
D005456:Fluorescent Dyes; D012235:Rhodamines; D020112:Rhodamine 123; D004317:Doxorubicin; D000255:Adenosine Triphosphate; D002118:Calcium; D016257:Fura-2