Calcium Signals Are Affected by Ciprofloxacin as a Consequence of Reduction of Mitochondrial DNA Content in Jurkat Cells

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 g/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 g/ml seriously affects cellular energy metabolism and calcium homeostasis.

Antibiotic-induced release of small extracellular vesicles (exosomes) with surface-associated DNA

“…In the present study, we investigated, the effects of the fluoroquinolone antibiotic ciprofloxacin that is used in the therapy of several human bacterial infections and is also applied in vitro against Mycoplasma contamination of cell cultures. The presence of a clinically relevant dose of ciprofloxacin has been reported to cause oxidative damage, mitochondrial dysfunction and mtDNA depletion in mammalian cells 27 – 29 . Here we report for the first time that ciprofloxacin induced the release of both mitochondrial and chromosomal DNA associated with the surface of EXOs.…”

Mitochondria as Oxidative Signaling Organelles in T-cell Activation: Physiological Role and Pathological Implications

“…Importantly, mtDNA depletion or mitochondrial uncoupling results in inhibition of the TCR-induced Ca 2? signal due to diminished mitochondrial membrane potential, and thus reduced ability to buffer and prolong Ca 2 influx (Hoth et al 2000;Koziel et al 2006). Moreover, T-cell activation-induced mitochondrial Ca 2?…”

Mitochondrial Reactive Oxygen Species Control T Cell Activation by Regulating IL-2 and IL-4 Expression: Mechanism of Ciprofloxacin-Mediated Immunosuppression

“…Numerous conflicting reports stated that ciprofloxacin activates or inhibits T cell activation-induced gene expression (e.g., for IFN-g, TNF-a, IL-2, and IL-4) (11)(12)(13)(14). Interestingly, as an inhibitor of bacterial topoisomerase II and an inducer of DNA double-strand breaks, ciprofloxacin was also shown to deplete the mitochondrial DNA (mtDNA) content, thus leading to mitochondrial dysfunction and retarded cellular growth (15)(16)(17).…”