title: Epigallocatechin-3-gallate induces oxidative phosphorylation by activating cytochrome c oxidase in human cultured neurons and astrocytes.
abstract: Mitochondrial dysfunction and resulting energy impairment have been identified as features of many neurodegenerative diseases. Whether this energy impairment is the cause of the disease or the consequence of preceding impairment(s) is still under discussion, however a recovery of cellular bioenergetics would plausibly prevent or improve the pathology. In this study, we screened different natural molecules for their ability to increase intracellular adenine triphosphate purine (ATP). Among them, epigallocatechin-3-gallate (EGCG), a polyphenol from green tea, presented the most striking results. We found that it increases ATP production in both human cultured astrocytes and neurons with different kinetic parameters and without toxicity. Specifically, we showed that oxidative phosphorylation in human cultured astrocytes and neurons increased at the level of the routine respiration on the cells pre-treated with the natural molecule. Furthermore, EGCG-induced ATP production was only blocked by sodium azide (NaN3) and oligomycin, inhibitors of cytochrome c oxidase (CcO; complex IV) and ATP synthase (complex V) respectively. These findings suggest that the EGCG modulates CcO activity, as confirmed by its enzymatic activity. CcO is known to be regulated differently in neurons and astrocytes. Accordingly, EGCG treatment is acting differently on the kinetic parameters of the two cell types. To our knowledge, this is the first study showing that EGCG promotes CcO activity in human cultured neurons and astrocytes. Considering that CcO dysfunction has been reported in patients having neurodegenerative diseases such as Alzheimer's disease (AD), we therefore suggest that EGCG could restore mitochondrial function and prevent subsequent loss of synaptic function.
authors.affiliation: MND and Neurodegenerative Diseases Research Group, Australian School of Advanced Medicine (ASAM), Macquarie University, Sydney, Australia.
authors.forename: Gloria
authors.initials: G
authors.lastname: Castellano-González
authors.affiliation: Department of Biological and Environmental Sciences, University of Gothenburg, Göteborg, Sweden.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Pichaud
authors.affiliation: School of Biotechnology and Biomolecular Sciences, The University of New South Wales, Sydney, Australia.
authors.forename: J William O
authors.initials: JW
authors.lastname: Ballard
authors.affiliation: Immusmol Pty Ltd., Pessac, France.
authors.forename: Alban
authors.initials: A
authors.lastname: Bessede
authors.affiliation: Topical Therapeutics Research Group, School of Medical Sciences, The University of New South Wales, Sydney, Australia.
authors.forename: Helder
authors.initials: H
authors.lastname: Marcal
authors.affiliation: MND and Neurodegenerative Diseases Research Group, Australian School of Advanced Medicine (ASAM), Macquarie University, Sydney, Australia.
authors.forename: Gilles J
authors.initials: GJ
authors.lastname: Guillemin
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D015153:Blotting, Western; D001921:Brain / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D019069:Cell Respiration / Q000187:drug effects; D002478:Cells, Cultured; D003576:Electron Transport Complex IV / Q000235:genetics / Q000378:metabolism*; D005333:Fetus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000494:pharmacology; D010084:Oxidation-Reduction; D010085:Oxidative Phosphorylation / Q000187:drug effects*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D018696:Neuroprotective Agents; D012333:RNA, Messenger; D000255:Adenosine Triphosphate; D002392:Catechin; C045651:epigallocatechin gallate; D003576:Electron Transport Complex IV
keywords: ATP; Gerotarget; cytochrome c oxidase; epigallocatechin-3-gallate; mitochondria; neurodegeneration