title: Coffee induces vascular endothelial growth factor (VEGF) expression in human neuroblastama SH-SY5Y cells.
abstract: Recent evidence indicates that hypoxia-inducible vascular endothelial growth factor (VEGF) has neurotrophic and neuroprotective effects on neuronal and glial cells. On the other hand, recent epidemiological studies showed that daily coffee consumption has been associated with a lower risk of several neuronal disorders. Therefore, we investigated the effect of coffee on VEGF expression in human neuroblastoma SH-SY5Y cells. We found that even low concentration of coffee (<2%) strongly induced VEGF expression via an activation of HIF-1α. The activation of HIF-1α by coffee was attributed to the coffee-dependent inhibition of prolyl hydroxylation of HIF1α, which is essential for proteolytic degradation of HIF-1α. However, no inhibition was observed at the catalytic activity in vitro. Coffee component(s) responsible for the activation of HIF-1α was not major constituents such as caffeine, caffeic acid, chlorogenic acid, and trigonelline, but was found to emerge during roasting process. The active component(s) was extractable with ethyl acetate. Our results suggest that daily consumption of coffee may induce VEGF expression in neuronal cells. This might be related to protective effect of coffee on neural disorders such as Alzheimer's disease and Parkinson's disease.
authors.affiliation: a Graduate School of Pharmaceutical Sciences, Keio University , Tokyo , Japan.
authors.forename: Shota
authors.initials: S
authors.lastname: Kakio
authors.affiliation: a Graduate School of Pharmaceutical Sciences, Keio University , Tokyo , Japan.
authors.forename: Megumi
authors.initials: M
authors.lastname: Funakoshi-Tago
authors.affiliation: b Department of Pharmaceutical and Health Sciences , Josai University , Saitama , Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Kobata
authors.affiliation: a Graduate School of Pharmaceutical Sciences, Keio University , Tokyo , Japan.
authors.forename: Hiroomi
authors.initials: H
authors.lastname: Tamura
mesh_terms: D000085:Acetates / Q000737:chemistry; D045744:Cell Line, Tumor; D003069:Coffee / Q000737:chemistry / Q000378:metabolism*; D005511:Food Handling; D055951:Functional Food; D005786:Gene Expression Regulation; D015972:Gene Expression Regulation, Neoplastic; D006358:Hot Temperature; D006801:Humans; D006900:Hydroxylation; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000819:agonists* / Q000378:metabolism; D009363:Neoplasm Proteins / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D009447:Neuroblastoma / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D000066829:Neuroprotection; D018696:Neuroprotective Agents / Q000302:isolation & purification / Q000378:metabolism*; D010936:Plant Extracts / Q000302:isolation & purification / Q000378:metabolism*; D011392:Proline / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D012997:Solvents / Q000737:chemistry; D042461:Vascular Endothelial Growth Factor A / Q000819:agonists* / Q000235:genetics / Q000378:metabolism
chemical_list: D000085:Acetates; D003069:Coffee; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D010936:Plant Extracts; D012997:Solvents; D042461:Vascular Endothelial Growth Factor A; C007650:ethyl acetate; D011392:Proline
keywords: Coffee; HIF-1a; Neurodegeneration; SH-SY5Y; VEGF