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l-3-n-butylphthalide alleviates hydrogen peroxide-induced apoptosis by PKC pathway in human neuroblastoma SK-N-SH cells

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Abstract

Alzheimer's disease (AD) is the most common form of dementia. Oxidative stress is one of the earliest events in the neurological and pathological changes of AD. l-3-n-butylphthalide (l-NBP), an anti-cerebral ischemia agent, has been shown a potential in AD treatment. In this study, we investigated the neuroprotective effect of l-NBP on hydrogen peroxide (H2O2)-induced apoptosis in human neuroblastoma SK-N-SH cells. H2O2 significantly reduced cell viability and increased the number of apoptotic-like cells, indicating that H2O2 induced neurotoxicity. In addition, real-time PCR and western blot studies showed that Bcl-2 and Bcl-w expressions were decreased, and Bax expression was increased with H2O2 treatment. Moreover, protein kinase C (PKC) α expression was down-regulated after H2O2 treatment. All of these phenotypes induced by H2O2 were markedly reversed by l-NBP. Pretreatment with l-NBP significantly increased cell viability of H2O2-damaged cells, and reduced H2O2 -induced neuronal apoptosis. l-NBP treatment at dose of 10 μM inhibited H2O2-induced down-regulation of Bcl-2, Bcl-w, and PKCα but also attenuated the overexpression of Bax. PKC inhibitor, calphostin C, significantly attenuated the protective effects of l-NBP. Our findings suggest that l-NBP may protect neurons against H2O2-induced apoptosis by modulating apoptosis-related genes and activating PKCα pathway.

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Acknowledgement

This study was supported by the grants from National Natural Sciences Foundation of China (No. 30973511), Natural Science Foundation of Beijing (No. 7093125), and National S&T Major Special Project on Major New Drug Innovation of China (2009ZX09303-003; 2008ZX09401-004).

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  1. Yanli Hu

    Present address: College of Pharmaceutical Sciences, Shihezi University, Shihezi, 832002, China

Authors and Affiliations

  1. Pharmacology Department, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, No.1, Xiannongtan Street, Beijing, 100050, China

    Ying Peng, Yanli Hu, Nan Feng, Ling Wang & Xiaoliang Wang

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  1. Ying Peng
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  2. Yanli Hu
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  3. Nan Feng
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  4. Ling Wang
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  5. Xiaoliang Wang
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Correspondence to Xiaoliang Wang.

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Ying Peng and Yanli Hu contributed equally to this work.

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Peng, Y., Hu, Y., Feng, N. et al. l-3-n-butylphthalide alleviates hydrogen peroxide-induced apoptosis by PKC pathway in human neuroblastoma SK-N-SH cells. Naunyn-Schmied Arch Pharmacol 383, 91–99 (2011). https://doi.org/10.1007/s00210-010-0575-9

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  • DOI: https://doi.org/10.1007/s00210-010-0575-9

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