Neuroprotective Effects of Kinetin Against Glutamate-Induced Oxidative Cytotoxicity in HT22 Cells: Involvement of Nrf2 and Heme Oxygenase-1
| Autor: | Wei Yunpeng, Ouyang Wuqing, Dan Liu, Chaoshuang Hao, Zheng Yin, Honglian Li |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Programmed cell death NF-E2-Related Factor 2 p38 mitogen-activated protein kinases Glutamic Acid Mitochondrion Biology Transfection Toxicology medicine.disease_cause Neuroprotection Mice 03 medical and health sciences Excitatory Amino Acid Agonists medicine Animals RNA Small Interfering Cell Line Transformed Membrane Potential Mitochondrial Neurons Cell Death Dose-Response Relationship Drug General Neuroscience Kinetin MAP Kinase Kinase Kinases Cell biology Heme oxygenase Protein Transport Neuroprotective Agents 030104 developmental biology Apoptosis Calcium Reactive Oxygen Species Cell Nucleolus Heme Oxygenase-1 Intracellular Oxidative stress Signal Transduction |
| Zdroj: | Neurotoxicity Research. 33:725-737 |
| ISSN: | 1476-3524 1029-8428 |
| DOI: | 10.1007/s12640-017-9811-0 |
| Popis: | Oxidative stress is considered as one of key factors related to Alzheimer's disease (AD), while kinetin (KT) has been reported to exert anti-oxidative activities as well as neuroprotective effects both in vivo and in vitro. Thus, in this study, the neuroprotective effects of KT against glutamate-induced oxidative toxicity in HT22 cells were investigated. To evaluate the anti-oxidative capabilities of KT itself, several anti-oxidative assays in vitro were conducted. To evaluate the neuroprotective effects of KT, the levels of intracellular reactive oxygen species (ROS) and calcium influx, mitochondrial membrane potential (MMP), and cell death were measured by flow cytometry. Nuclear translocation of apoptosis inducing factor (AIF) and content of intracellular ATP were also determined. In addition, the phosphorylation levels of apoptosis signal-regulating kinase 1 (ASK-1), c-Jun N-terminal kinase (JNK), and p38 mitogen-activated protein kinases (p38) were evaluated as well. Besides, nuclear translocation of nuclear factor-E2-related factor 2 (Nrf2) and the expression of heme oxygenase-1 (HO-1) were also examined to reveal underlying mechanisms. Results showed that KT rescued cell death, and suppressed the accumulation of intracellular ROS and the increase of intracellular calcium influx. In addition, KT maintained normal function of mitochondria and inhibited the phosphorylation of ASK-1, JNK, and p38. KT also promoted nuclear translocation of Nrf2 and enhanced the expression of HO-1 both at protein and mRNA level. Importantly, blockage of Nrf2 almost completely abolished the neuroprotective effects of KT, while blockage of HO-1 expression partly neutralized its neuroprotective effects. Our results indicated that KT can protect HT22 cells from glutamate-induced cell death by activating Nrf2 pathway and inducing expression of HO-1, suggesting KT might be a drug candidate for treatment of AD and other neurodegenerative disorders related to oxidative stress. |
| Databáze: | OpenAIRE |
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