Mercuric chloride induces a stress response in cultured astrocytes characterized by mitochondrial uptake of iron

Mercury exerts a variety of toxic effects on both neurons and glia. Mercury induces aberrations in microtubules, ion channels and mitochondria presuma bly by binding to sulfhydryl groups. Indirect evidence further suggests tha t mercury targeted to mitochondria may induce iron-catalyzed oxygen radical production. We have previously shown that the mitochondria of astrocytes s ubjected to oxidative stress accumulate redox active transition metals that may catalyze the formation of cytotoxic oxygen free radicals. In the prese nt study we have investigated the effect of mercuric chloride on astrocytes in monolayer culture in order to determine whether mercury accumulates in astrocytic mitochondria and whether mercury exposure triggers a stress resp onse-associated uptake of iron. Our results indicate that mercuric chloride exposure initiates the constellation of changes in mitochondrial structure that typifies the response of these cells to oxidative stress. Energy disp ersive Xray microspectroscopy demonstrates that these altered mitochondria concentrate both mercury and iron. Concurrent with these changes, mercuric chloride treatment activates transcription of the heme oxygenase-1 (HO-1) g ene in a dose dependent manner, further indicating an oxidative stress resp onse. Thus, mercury-induced stress may transform innocuous astrocytes into potentially lethal sources of cytotoxic oxygen free radicals. (C) 1998, Int ox Press, Inc.