Calcium signals are affected by ciprofloxacin as a consequence of reduction of mitochondrial DNA content in Jurkat cells

Antimicrob Agents Chemother. 2006 May;50(5):1664-71. doi: 10.1128/AAC.50.5.1664-1671.2006.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / analysis
  • Adenosine Triphosphate / metabolism
  • Anti-Infective Agents / pharmacology*
  • Autoradiography
  • Blotting, Southern
  • Calcium Signaling / drug effects*
  • Ciprofloxacin / pharmacology*
  • Cytosol / metabolism
  • DNA Probes
  • DNA, Mitochondrial / metabolism*
  • Electrophoresis, Agar Gel
  • Flow Cytometry
  • Humans
  • Jurkat Cells
  • Membrane Potentials / drug effects
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • Oxygen Consumption
  • T-Lymphocytes / cytology
  • T-Lymphocytes / drug effects*
  • T-Lymphocytes / metabolism

Substances

  • Anti-Infective Agents
  • DNA Probes
  • DNA, Mitochondrial
  • Ciprofloxacin
  • Adenosine Triphosphate