Calcium signals are affected by ciprofloxacin as a consequence of reduction of mitochondrial DNA content in Jurkat cells.
The effects of ciprofloxacin on mitochondrial DNA (mtDNA) content, oxygen consumption, mitochondrial membrane potential, cellular ATP formation, and capacitative Ca(2+) entry into Jurkat cells were investigated. In cells incubated for several days with 25 mug/ml ciprofloxacin, a 60% reduction of mtDNA content, inhibition of the respiratory chain, and a significant decrease in mitochondrial membrane potential were observed. These changes led to a decrease in the calcium buffering capacity of mitochondria which, in turn, resulted in a gradual inhibition of the capacitative Ca(2+) entry. On days 4, 7, and 11 of incubation with ciprofloxacin, the initial rates of Ca(2+) entry were reduced by 33%, 50%, and 50%, respectively. Ciprofloxacin caused a transient decrease in the cellular capability for ATP formation. In cells incubated for 15 min with glucose, pyruvate, and glutamine as exogenous fuel, ciprofloxacin reduced ATP content by 16% and 35% on days 4 and 7, respectively, of incubation with the drug. However, on day 11 of incubation with ciprofloxacin, a recovery of cellular ATP formation was observed. In conclusion, long-term exposure of Jurkat cells to ciprofloxacin at a concentration of 25 mug/ml seriously affects cellular energy metabolism and calcium homeostasis.
Kozieł
Rafał
R
Nencki Institute of Experimental Biology, Pasteura 3, 02-093 Warsaw, Poland.
Zabłocki
Krzysztof
K
Duszyński
Jerzy
J
D000255:Adenosine Triphosphate / Q000032:analysis / Q000378:metabolism; D000890:Anti-Infective Agents / Q000494:pharmacology*; D001345:Autoradiography; D015139:Blotting, Southern; D020013:Calcium Signaling / Q000187:drug effects*; D002939:Ciprofloxacin / Q000494:pharmacology*; D003600:Cytosol / Q000378:metabolism; D015342:DNA Probes; D004272:DNA, Mitochondrial / Q000378:metabolism*; D004587:Electrophoresis, Agar Gel; D005434:Flow Cytometry; D006801:Humans; D019169:Jurkat Cells; D008564:Membrane Potentials / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D010101:Oxygen Consumption; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
D000890:Anti-Infective Agents; D015342:DNA Probes; D004272:DNA, Mitochondrial; D002939:Ciprofloxacin; D000255:Adenosine Triphosphate