Comparative study of hydrogen peroxide- and 4-hydroxy-2-nonenal-induced cell death in HT22 cells.
Several studies have indicated that lipid peroxidation often occurs in response to oxidative stress, and that many aldehydic products including 4-hydroxy-2-nonenal (HNE) are formed when lipid hydroperoxides break down. In order to clarify the mechanism of oxidative stress-induced neuronal death in the nervous system, we investigated H(2)O(2)- and HNE-induced cell death pathways in HT22 cells, a mouse hippocampal cell line, under the same experimental conditions. Treatment with H(2)O(2) and HNE decreased the viability of these cells in a time- and concentration-dependent manner. In the cells treated with H(2)O(2), significant increases in the immunoreactivities of DJ-1 and nuclear factor-kappaB (NF-kappaB) subunits (p65 and p50) were observed in the nuclear fraction. H(2)O(2) also induced an increase in the intracellular concentration of Ca(2+), and cobalt chloride (CoCl(2)), a Ca(2+) channel inhibitor, suppressed the H(2)O(2)-induced cell death. In HNE-treated cells, none of these phenomena were observed; however, HNE adduct proteins were formed after exposure to HNE, but not to H(2)O(2). N-Acetyl-L-cysteine (NAC) suppressed both HNE-induced cell death and HNE-induced expression of HNE adduct proteins, whereas H(2)O(2)-induced cell death was not affected. These findings suggest that the mechanisms of cell death induced by H(2)O(2) different from those induced by HNE in HT22 cells, and that HNE adduct proteins play an important role in HNE-induced cell death. It is also suggested that the pathway for H(2)O(2)-induced cell death in HT22 cells does not involve HNE production.
Ishimura
Atsushi
A
Research Unit of Pharmacology, Department of Clinical Pharmacy, College of Pharmacy, Nihon University, 7-7-1 Narashinodai, Funabashi-shi, Chiba 274-8555, Japan.
Ishige
Kumiko
K
Taira
Takahiro
T
Shimba
Shigeki
S
Ono
Shin-Ichi
S
Ariga
Hiroyoshi
H
Tezuka
Masakatsu
M
Ito
Yoshihisa
Y
D000111:Acetylcysteine / Q000494:pharmacology; D000447:Aldehydes / Q000633:toxicity*; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects*; D045744:Cell Line, Tumor; D003035:Cobalt / Q000494:pharmacology; D005434:Flow Cytometry; D016166:Free Radical Scavengers / Q000494:pharmacology; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D016328:NF-kappa B / Q000502:physiology; D009474:Neurons / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology; D016877:Oxidants / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects; D011419:Propidium; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013778:Tetrazolium Salts; D013844:Thiazoles
D000447:Aldehydes; D016166:Free Radical Scavengers; D016328:NF-kappa B; D018696:Neuroprotective Agents; D016877:Oxidants; D017382:Reactive Oxygen Species; D013778:Tetrazolium Salts; D013844:Thiazoles; D011419:Propidium; D003035:Cobalt; D006861:Hydrogen Peroxide; D007770:L-Lactate Dehydrogenase; C022616:thiazolyl blue; C018021:cobaltous chloride; C027576:4-hydroxy-2-nonenal; D002118:Calcium; D000111:Acetylcysteine