Is the ATP-dependent protection of lysosomes against osmotic lysis a function of the lysosomal proton pump.
Rat liver lysosomes have been used to characterize further the effects of ATP on lysosomal stability during incubation at 37 degrees C at hypo-osmolarity. As previously reported, when the osmotically-supporting solute is the salt of a strong base (K+), ATP protects against lysis during incubation. However, if the osmotically-supporting solute is the salt of a weak base, e.g. Tris HCl or NH4Cl, ATP actually promotes lysis during incubation. Thus, ATP can exert destabilizing as well as protective effects on lysosomes. The destabilizing effect is eliminated by protonophores. The protective effect in the presence of potassium salts is not eliminated by protonophores. Moreover, when incubation is in the presence of a salt of a weak base, protonophores actually cause an ATP-dependent protective effect to be established. The destabilizing effect occurs at 37 degrees C, but not at 0 degrees C. The Mg++-dependence of the destabilizing effect was found to be similar to that found earlier for the ATP-dependent protective effect, insofar as only 1 mM MgCl2 in the presence of 1mM EDTA is sufficient for nearly maximal stimulation of both effects. The destabilizing effect may result from a H+ ion gradient across the lysosomal membrane which is maintained by the lysosomal ATP-dependent proton pump. The protective effect, on the other hand, does not depend on such a gradient being maintained; on the contrary, protonophores appear to act as enablers of the protective effect. The question that remains to be answered is: does the protective effect derive in some way from the same ATP-driven mechanism which constitutes the proton pump? Some possible answers to this question are considered.
Ruth
R C
RC
Department of Medicine, George Washington University, Washington, D.C. 20037.
Weglicki
W B
WB
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D007476:Ionophores / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008247:Lysosomes / Q000187:drug effects* / Q000378:metabolism; D008274:Magnesium / Q000494:pharmacology; D008297:Male; D009997:Osmotic Pressure; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D007476:Ionophores; D000255:Adenosine Triphosphate; D008274:Magnesium; D011188:Potassium