title: Hyperforin changes the zinc-storage capacities of brain cells.
abstract: In vitro and in vivo experiments were carried out to investigate the consequences on brain cells of a chronic treatment with hyperforin, a plant extract known to dissipate the mitochondrial membrane potential and to release Zn(2+) and Ca(2+) from these organelles. Dissociated cortical neurons were grown in a culture medium supplemented with 1 μM hyperforin. Live-cell imaging experiments with the fluorescent probes FluoZin-3 and Fluo-4 show that a 3 day-hyperforin treatment diminishes the size of the hyperforin-sensitive pools of Ca(2+) and Zn(2+) whereas it increases the size of the DTDP-sensitive pool of Zn(2+) without affecting the ionomycin-sensitive pool of Ca(2+). When assayed by quantitative PCR the levels of mRNA coding for metallothioneins (MTs) I, II and III were increased in cortical neurons after a 3 day-hyperforin treatment. This was prevented by the zinc chelator TPEN, indicating that the plant extract controls the expression of MTs in a zinc-dependent manner. Brains of adult mice who received a daily injection (i.p.) of hyperforin (4 mg/kg/day) for 4 weeks had a higher sulphur content than control animals. They also exhibited an enhanced expression of the genes coding for MTs. However, the long-term treatment did not affect the brain levels of calcium and zinc. Based on these results showing that hyperforin influences the size of the internal pools of Zn(2+), the expression of MTs and the brain cellular sulphur content, it is proposed that hyperforin changes the Zn-storage capacity of brain cells and interferes with their thiol status.
authors.affiliation: UMR CNRS 5249, Grenoble, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Gibon
authors.forename: Pierre
authors.initials: P
authors.lastname: Richaud
authors.forename: Alexandre
authors.initials: A
authors.lastname: Bouron
mesh_terms: D015082:2,2'-Dipyridyl / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000166:cytology* / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D002614:Chelating Agents / Q000494:pharmacology; D004220:Disulfides / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005029:Ethylenediamines / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D015759:Ionomycin / Q000494:pharmacology; D008297:Male; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000187:drug effects*; D016877:Oxidants / Q000494:pharmacology; D010696:Phloroglucinol / Q000031:analogs & derivatives* / Q000494:pharmacology; D013455:Sulfur / Q000378:metabolism; D013729:Terpenes / Q000494:pharmacology*; D013997:Time Factors; D015032:Zinc / Q000378:metabolism*
chemical_list: D002614:Chelating Agents; D004220:Disulfides; D005029:Ethylenediamines; D016877:Oxidants; D013729:Terpenes; C001105:2,2'-dipyridyl disulfide; D015082:2,2'-Dipyridyl; D015759:Ionomycin; D013455:Sulfur; D010696:Phloroglucinol; D020782:Matrix Metalloproteinases; D015032:Zinc; C044387:N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine; C001654:hyperforin; D002118:Calcium