Differential effects of α-tocopherol and N-acetyl-cysteine on advanced glycation end product-induced oxidative damage and neurite degeneration in SH-SY5Y cells

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

卷:1822

Article

Pazdro, Robert¹  Burgess, John R.¹ 

[1] Purdue Univ, Dept Nutr Sci, W Lafayette, IN 47907 USA

关键词: Advanced glycation end product;    Diabetes;    Oxidative stress;    Vitamin E;    Neuropathy;    N-acetyl cysteine;   

DOI  :  10.1016/j.bbadis.2012.01.003

来源: Elsevier

【 摘 要 】

Advanced glycation end products (AGES) result from non-enzymatic glycation of proteins and cause cellular oxidative stress in a nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-dependent manner. Due to these effects, AGEs are implicated as a causal factor in diabetic complications. Several antioxidants, including vitamin E, improve cell viability and diminish markers of oxidative damage in cells exposed to AGEs. However, vitamin E has been studied in cell culture systems with primary focus on apoptosis and lipid peroxidation, while its influences on AGE-induced protein and DNA oxidation, intracellular antioxidant status and cell morphology remain largely unknown. Here, we verify the suppression of AGE-induced cell death and lipid peroxidation by 200 mu M alpha-tocopherol in SH-SY5Y cells. We report the partial inhibition of DNA oxidation and a decrease in protein carbonyl formation by alpha-tocopherol with no effects on intracellular GSH concentrations. We observed that 2 mM N-acetyl cysteine (NAC) also had a suppressive effect on DNA and protein oxidation, but unlike alpha-tocopherol, it caused a marked increase in intracellular GSH. Finally, we compared the ability of both antioxidants to maintain neurites in SH-SY5Y cells and found that alpha-tocopherol had no effect on neurite loss due to AGES, while NAC fully maintained cell morphology. Thus, while alpha-tocopherol suppressed AGE-induced macromolecule damage, it was ineffective against neurite degeneration. These results may implicate thiol oxidation and maintenance as a major regulator of neurite degeneration in this model. (C) 2012 Elsevier B.V. All rights reserved.

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