title: The combination of 1α,25dihydroxyvitaminD3 with resveratrol improves neuronal degeneration by regulating endoplasmic reticulum stress, insulin signaling and inhibiting tau hyperphosphorylation in SH-SY5Y cells.
abstract: Endoplasmic reticulum (ER) stress is a critical factor involved in the pathogenesis of Alzheimer's disease (AD). Vitamin D and resveratrol are two nutritional factors that have reported neuroprotective effects, and findings from cellular models suggest that resveratrol could potentiate vitamin D's effects. We aimed to determine the effects of vitamin D & resveratrol on ER stress mediated neurodegeneration and whether synergistic effects existed. Tunicamycin and Aβ25-35 was utilized to induce ER stress in SH-SY5Y cells, cells were then incubated with vitamin D and resveratrol. The combination of vitamin D & resveratrol completely reversed tunicamycin and Aβ25-35 induced cytotoxicity in SH-SY5Y cells, as well as elevation in ER stress markers (i.e.GRP78, p-eIF2α and CHOP), insulin signaling disruption (i.e. elevation in p-IRS-1serine307 and reduction in p-Akt serine473) and tau phosphorylation (i.e. reduction in p-GSK3β serine9, and elevation in p-Tau serine396 &404). Further studies are required to clarify whether the observed synergistic effects in the present study would also existed in vivo, this will lay scientific foundation whether the combination of vitamin D with resveratrol might be an effective maneuver in the treatment of AD in human subjects.
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health, Soochow University, No. 199 Renai Road, Suzhou, 215123, PR China.
authors.forename: Jinbo
authors.initials: J
authors.lastname: Cheng
authors.affiliation: Department of Breast Surgery, Zhejiang Cancer Hospital, Hangzhou, 310022, Zhejiang, PR China.
authors.forename: Xianghou
authors.initials: X
authors.lastname: Xia
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health, Soochow University, No. 199 Renai Road, Suzhou, 215123, PR China.
authors.forename: Yehua
authors.initials: Y
authors.lastname: Rui
authors.affiliation: Department of Labor Hygiene and Environmental Health, School of Public Health, Soochow University, No. 199 Renai Road, Suzhou, 215123, PR China.
authors.forename: Zengli
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health, Soochow University, No. 199 Renai Road, Suzhou, 215123, PR China.
authors.forename: Liqiang
authors.initials: L
authors.lastname: Qin
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health, Soochow University, No. 199 Renai Road, Suzhou, 215123, PR China.
authors.forename: Shufen
authors.initials: S
authors.lastname: Han
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health, Soochow University, No. 199 Renai Road, Suzhou, 215123, PR China; Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Disease, Soochow University, No. 199 Ren'ai Road, Suzhou, 215123, PR China. Electronic address: zhxwan@suda.edu.cn.
authors.forename: Zhongxiao
authors.initials: Z
authors.lastname: Wan
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002117:Calcitriol / Q000494:pharmacology*; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D009447:Neuroblastoma / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010446:Peptide Fragments / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D000077185:Resveratrol; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013267:Stilbenes / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014415:Tunicamycin / Q000009:adverse effects; D014815:Vitamins / Q000494:pharmacology; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D000900:Anti-Bacterial Agents; D000975:Antioxidants; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D007328:Insulin; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D012333:RNA, Messenger; D013267:Stilbenes; D014815:Vitamins; C074636:amyloid beta-protein (25-35); D016875:tau Proteins; D014415:Tunicamycin; D002117:Calcitriol; D000077185:Resveratrol
keywords: Alzheimer's disease; Amyloid β; Insulin resistance; PERK; Polyphenol