Reduction of H2O2-evoked, intracellular calcium increases in the rat N18-RE-105 neuronal cell line by pretreatment with an electrophilic antioxidant inducer.
Pretreatment of the neuronal cell line N18-RE-105 with the antioxidant enzyme inducer dimethyl fumarate (DMF) reduced cell death elicited by H2O2 (50 mM for 1 h) as measured 24 h after H2O2 washout. Oxidants like H2O2 may contribute to cell death by increasing intracellular ionized calcium ([Ca2+]i), suggesting that DMF may in part confer protection by altering H2O2-induced [Ca2+]i signals. To examine this possibility, we measured [Ca2+]i of fura-2-loaded cultures of DMF- and vehicle-pretreated cells during H2O2 superfusion. H2O2 exposure induced a delayed [Ca2+]i increase that was significantly lower in DMF-pretreated cells than controls. Elevation of extracellular cystine also reduced the H2O2 induced [Ca2+]i elevation. Thus, antioxidant upregulation may contribute to protection during oxidative stress by stabilizing [Ca2+]i. However, since oxidative stress may induce cytotoxicity by multiple pathways, [Ca2+]i stabilization may not be the only mechanism responsible for the protective effect of DMF.
Su
J Y
JY
Department of Psychiatry University of British Columbia, Vancouver, Canada.
Duffy
S
S
Murphy
T H
TH
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D003553:Cystine / Q000037:antagonists & inhibitors; D000069462:Dimethyl Fumarate; D004790:Enzyme Induction; D005110:Extracellular Space / Q000378:metabolism; D005650:Fumarates / Q000494:pharmacology*; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D007425:Intracellular Membranes / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D009994:Osmolar Concentration; D016877:Oxidants / Q000494:pharmacology*; D010088:Oxidoreductases / Q000378:metabolism*; D051381:Rats; D014407:Tumor Cells, Cultured
D005650:Fumarates; D016877:Oxidants; D003553:Cystine; D006861:Hydrogen Peroxide; D010088:Oxidoreductases; D000069462:Dimethyl Fumarate; D002118:Calcium