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 presumably by binding to sulfhydryl groups. Indirect evidence further suggests that mercury targeted to mitochondria may induce iron-catalyzed oxygen radical production. We have previously shown that the mitochondria of astrocytes subjected to oxidative stress accumulate redox active transition metals that may catalyze the formation of cytotoxic oxygen free radicals. In the present 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 response-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 dispersive 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) gene in a dose dependent manner, further indicating an oxidative stress response. Thus, mercury-induced stress may transform innocuous astrocytes into potentially lethal sources of cytotoxic oxygen free radicals.
Brawer
J R
JR
Department of Anatomy and Cell Biology, McGill University, Montreal, Quebec, Canada.
McCarthy
G F
GF
Gornitsky
M
M
Frankel
D
D
Mehindate
K
K
Schipper
H M
HM
D000818:Animals; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D002478:Cells, Cultured; D004577:Electron Probe Microanalysis; D005609:Free Radicals; D007501:Iron / Q000378:metabolism*; D008627:Mercuric Chloride / Q000633:toxicity*; D008854:Microscopy, Electron; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism
D005609:Free Radicals; D017382:Reactive Oxygen Species; D008627:Mercuric Chloride; D007501:Iron