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Chronic Low‐Dose Oxidative Stress Induces Caspase‐3‐Dependent PKCδ Proteolytic Activation and Apoptosis in a Cell Culture Model of Dopaminergic Neurodegeneration
Author(s) -
Carvour Martha,
Song Chunjuan,
Kaul Siddharth,
Anantharam Vellareddy,
Kanthasamy Anumantha,
Kanthasamy Arthi
Publication year - 2008
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1432.020
Subject(s) - neurodegeneration , oxidative stress , programmed cell death , dopaminergic , apoptosis , neurotoxicity , caspase , microbiology and biotechnology , chemistry , neuroprotection , caspase 3 , trolox , pharmacology , biology , biochemistry , neuroscience , medicine , dopamine , toxicity , disease , organic chemistry , antioxidant capacity
Oxidative stress has been implicated as a key event in the degenerative process of dopaminergic neurons; however, the cellular mechanisms underlying chronic oxidative stress–induced neurodegeneration remain to be established. In this study, N27 cells, a dopaminergic neuronal cell line derived from rat mesencephalon, exposed to low doses of H 2 O 2 (0–30 μM for 12–24 hr) exhibited dose‐ and time‐dependent increases in cytotoxicity and ROS generation. In addition, the H 2 O 2 ‐induced neurotoxicity was accompanied by increased caspase‐3 activity and PKCδ cleavage. Notably, treatment with antioxidants Trolox and MnTBAP or PKCδ cleavage inhibitor z‐DIPD‐fmk significantly protected against oxidative stress–induced apoptotic cell death. These results demonstrate that the N27 cell line is a useful model for the study of the chronic low‐dose oxidative stress–induced apoptotic cell death cascade and that caspase‐3‐dependent PKCδ proteolytic activation may be important in the apoptotic process in dopaminergic neurons undergoing chronic oxidative insult.