Hamdan Medical Journal (previously the Journal of Medical Sciences)

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Caffeine Impairs HL-60 Cellular Respiration

Eyone Jones, Harvey S. Penefsky, Abdul-Kader Souid
Published in : Journal of Medical Sciences ; Vol 2, No 2 (2009)
DOI : 10.2174/1996327000902020061


We investigated the effect of caffeine on mitochondrial O2 consumption in human promyelocytic leukemia (HL-60) cells. A phosphorescence analyzer that measures O2 concentrations in cell suspensions as function of time was used for this purpose. O2 concentrations were determined from the phosphorescence of Pd phosphor, calculated by fitting the phosphorescence decays to exponentials. In sealed vials, O2 concentrations in the cell suspensions containing glucose declined linearly with time, showing zero-order kinetics for O2 consumption. NaCN inhibited O2 consumption, confirming the oxidation occurred in the mitochondrial respiratory chain. A rapid decline in the rate of respiration was observed when 50 μM to 4.0 mM caffeine was added to HL-60 cells in cell growth media (containing 1.41 mM Ca2+) or phosphate-buffered-salts (containing 0.91 mM Ca2+). This reversible inhibition was blocked by verapamil and was concentration-dependent, reaching a plateau (43 + 7% inhibition) at 50 μM caffeine. The inhibition was not observed when cellular Ca2+ stores were depleted. T-cell lymphoma (Jurkat) cells and isolated mitochondria were less sensitive to caffeine. Thus, caffeine is a potent inhibitor of HL-60 respiration. This effect is possibly mediated by Ca2+-flooding into the cytosol and neighboring mitochondria.

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