Cell damage caused by ATP depletion is reduced by magnesium and nickel in human fibroblasts--a non-specific calcium antagonism?
Calcium has been suggested to be the final common mediator of cell damage, but conflicting reports to prove this hypothesis have appeared. In order to elucidate the role of calcium in cell damage caused by ATP depletion, the effect of addition of calcium channel blockers (verapamil and nitrendipine) and non-specific antagonists (magnesium and nickel) was investigated in a model system of quiescent fibroblasts. ATP depletion was induced by metabolic inhibitors and the cell damage was assessed by the release of lactate dehydrogenase. Verapamil and nitrendipine did not protect the cells during ATP depletion, whereas a high concentration of Mg2+ (3-10 mmol/l) or a lower concentration of Ni2+ (0.5-1.0 mmol/l) reduced the cell damage considerably. An increased extracellular concentration of Ca2+ resulted in augmented cell damage. The effect of Mg2+ and Ni2+ was not due to an interference with the metabolic inhibitors or a reduction of the energy consumption. Both Ni2+ and Mg2+ were able to counteract the cell damage induced by entrance of Ca2+ after addition of the ionophore A23187. However, Mg2+ and Ni2+ were deleterious for the cells during ATP regeneration after an initial ATP decrease. These results indicate that a non-specific antagonism of Ca2+ may reduce cell damage, and, therefore, that Ca2+ may have an important role in cell damage, but also that a non-specific antagonism of Ca2+ during regeneration of ATP depleted cells is deleterious.
Kristensen
S R
SR
Department of Clinical Chemistry, Odense University Hospital, Denmark.
D000255:Adenosine Triphosphate / Q000502:physiology*; D002118:Calcium / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D002460:Cell Line; D004492:Edetic Acid / Q000494:pharmacology; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D015636:Magnesium Chloride / Q000494:pharmacology*; D009532:Nickel / Q000494:pharmacology*
D015636:Magnesium Chloride; C022838:nickel chloride; D009532:Nickel; D000255:Adenosine Triphosphate; D004492:Edetic Acid; D007770:L-Lactate Dehydrogenase; D002118:Calcium