CYTOPROTECTION AGAINST MEROCYANINE 540-SENSITIZED PHOTOINACTIVATION OF THE NA-ADENOSINE TRIPHOSPHATASE IN LEUKEMIA-CELLS - GLUTATHIONE AND SELENOPEROXIDASE INVOLVEMENT(,K+)

When irradiated with broad-band visible light in the presence of meroc yanine 540 (MC540), murine leukemia L1210 cells grown under selenium-d eficient conditions (Se(-) cells) accumulated lipid hydroperoxides and lost viability more rapidly than selenium-satisfied controls (Se(+) c ells). These findings suggest that cytoprotection against photoperoxid ation and photokilling is mediated at least in part by selenoperoxidas e (SePX) action. Similar protection against photoinactivation of an in trinsic membrane enzyme, the Na+,K+-ATPase, has been observed. Thus, i rradiation of MC540-sensitized Se(-) cells resulted in an immediate an d progressive inactivation of ouabain-sensitive Na+,K+-ATPase; by cont rast, activity loss in Se(+) cells was preceded by a prominent lag. En zyme photoinactivation in Se(-) cells was inhibited by ebselen, an SeP X mimetic, confirming that SePX(s) is (are) involved in natural protec tion. Desferrioxamine treatment (iron sequestration/inactivation) resu lted in higher hydroperoxide levels and slower Na+,K+-ATPase inactivat ion during MC540/light exposure, whereas ferric-8-hydroxquinoline trea tment (iron supplementation) had the opposite effect. Thus, iron appea rs to play an important role in both of these processes. In contrast, photoinactivation of another intrinsic enzyme in L1210 cells, acetylch olinesterase (AChE), was unaffected by selenium or iron manipulation. On the basis of these findings, we propose that lipid peroxidation pla ys an important role in the photoinactivation of Na+,K+-ATPase, but no t AChE. This is consistent with the fact that Na+,K+-ATPase's active s ite lies within the membrane bilayer, whereas AChE's active site lies outside the bilayer.