title: Pterostilbene attenuates high glucose-induced oxidative injury in hippocampal neuronal cells by activating nuclear factor erythroid 2-related factor 2.
abstract: In the present study, neuroblastoma (SH-SY5Y) cells were used to investigate the mechanisms mediating the potential protective effects of pterostilbene (PTE) against mitochondrial metabolic impairment and oxidative stress induced by hyperglycemia for mimicking the diabetic encephalopathy. High glucose medium (100mM) decreased cellular viability after 24h incubation which was evidenced by: (i) reduced mitochondrial complex I and III activities; (ii) reduced mitochondrial cytochrome C; (iii) increased reactive oxygen species (ROS) generation; (iv) decreased mitochondrial membrane potential (ΔΨm); and (v) increased lactate dehydrogenase (LDH) levels. PTE (2.5, 5, and 10μM for 24h) was nontoxic and induced the nuclear transition of Nrf2. Pretreatment of PTE (2.5, 5, and 10μM for 2h) displayed a dose-dependently neuroprotective effect, as indicated by significantly prevented high glucose-induced loss of cellular viability, generation of ROS, reduced mitochondrial complex I and III activities, reduced mitochondrial cytochrome C, decreased ΔΨm, and increased LDH levels. Moreover, the levels of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1) and glutathione S-transferase (GST) were elevated after PTE treatment. In addition, the elevation of nuclear Nrf2 by PTE treatment (10μM for 2h) was abolished by Nrf2 siRNA. Importantly, Nrf2 siRNA induced the opposite changes in mitochondrial complex I and III activities, mitochondrial cytochrome C, reactive species generation, ΔΨm, and LDH. Overall, the present findings were the first to show that pterostilbene attenuated high glucose-induced central nervous system injury in vitro through the activation of Nrf2 signaling, displaying protective effects against mitochondrial dysfunction-derived oxidative stress.
authors.affiliation: Department of Biomedical Engineering, The Fourth Military Medical University, 169 Changle West Road, Xi'an 710032, China; Department of Thoracic and Cardiovascular Surgery, Affiliated Drum Tower Hospital of Nanjing University Medical School, 321 Zhongshan Road, Nanjing 210008, Jiangsu, China. Electronic address: yang200214yy@163.com.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Thoracic Surgery, Tangdu Hospital, The Fourth Military Medical University, 1 Xinsi Road, Xi'an 710038, China.
authors.forename: Chongxi
authors.initials: C
authors.lastname: Fan
authors.affiliation: Graduate Management Team, The Fourth Military Medical University, 169 Changle West Road, Xi'an 710032, China.
authors.forename: Bodong
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of Thoracic Surgery, Tangdu Hospital, The Fourth Military Medical University, 1 Xinsi Road, Xi'an 710038, China.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Ma
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, Affiliated Drum Tower Hospital of Nanjing University Medical School, 321 Zhongshan Road, Nanjing 210008, Jiangsu, China.
authors.forename: Dongjin
authors.initials: D
authors.lastname: Wang
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, Affiliated Drum Tower Hospital of Nanjing University Medical School, 321 Zhongshan Road, Nanjing 210008, Jiangsu, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Gong
authors.affiliation: Department of Thoracic Surgery, Tangdu Hospital, The Fourth Military Medical University, 1 Xinsi Road, Xi'an 710038, China.
authors.forename: Shouyin
authors.initials: S
authors.lastname: Di
authors.affiliation: Department of Aerospace Medicine, The Fourth Military Medical University, 169 Changle West Road, Xi'an 710032, China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Jiang
authors.affiliation: Department of Biomedical Engineering, The Fourth Military Medical University, 169 Changle West Road, Xi'an 710032, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Biomedical Engineering, The Fourth Military Medical University, 169 Changle West Road, Xi'an 710032, China.
authors.forename: Tian
authors.initials: T
authors.lastname: Li
authors.affiliation: Department of Biomedical Engineering, The Fourth Military Medical University, 169 Changle West Road, Xi'an 710032, China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Department of Biomedical Engineering, The Fourth Military Medical University, 169 Changle West Road, Xi'an 710032, China. Electronic address: erpingluo@126.com.
authors.forename: Erping
authors.initials: E
authors.lastname: Luo
mesh_terms: D045744:Cell Line, Tumor; D045304:Cytochromes c / Q000235:genetics / Q000378:metabolism; D042967:Electron Transport Complex I / Q000235:genetics / Q000378:metabolism; D014450:Electron Transport Complex III / Q000235:genetics / Q000378:metabolism; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology*; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000235:genetics / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects / Q000235:genetics; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects* / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D013267:Stilbenes / Q000494:pharmacology*
chemical_list: D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D013267:Stilbenes; C107773:pterostilbene; D045304:Cytochromes c; D007770:L-Lactate Dehydrogenase; D042967:Electron Transport Complex I; D014450:Electron Transport Complex III; D005947:Glucose
keywords: High glucose; Neuroprotection; Nuclear factor erythroid 2-related factor 2 signaling; Oxidative stress; Pterostilbene