title: A catechin-enriched green tea extract prevents glucose-induced survival reduction in Caenorhabditis elegans through sir-2.1 and uba-1 dependent hormesis.
abstract: Hyperglycemia is a hallmark of diabetes mellitus which leads to the onset of complications in the long term. Green tea through its high content of polyphenolic catechins, on the other hand, is suggested to prevent or at least delay such detrimental complications. In the present study we fed the nematode Caenorhabditis elegans on a liquid medium supplemented with 10mM glucose in the absence or presence of a catechin-enriched green tea extract (CEGTE). After exposure of young adults for 48h survival was subsequently measured under heat stress at 37°C. Whereas CEGTE at 0.01% did not affect the survival of wild type nematodes, it completely reversed the glucose-induced survival reduction. Those effects were not achieved through the monomeric catechins included in CEGTE. RNA interference (RNAi) for sir-2.1 not only prevented the survival extension by CEGTE under simultaneous glucose exposure but also caused a further reduction of survival. Likewise, the knockdown of uba-1, encoding the only E1-ubiquitin-activating enzyme in C. elegans, proved that UBA-1 is essential for the survival extension by CEGTE and that its loss of function changes CEGTE from a survival extending into a survival reducing extract. Stimulation of the proteasome by CEGTE was finally proven through measurements of the proteolytic cleavage of a fluorogenic peptide substrate. To conclude, our studies provide evidence that CEGTE reverses glucose-induced damage in C. elegans through activation of adaptive responses mediated by SIR-2.1 and proteasomal degradation. The hormetic mode of action is revealed by a reduction of survival once the adaptive processes were blocked.
authors.affiliation: Molecular Nutrition Research, Interdisciplinary Research Center, Justus-Liebig-University of Giessen, Heinrich-Buff-Ring 26-32, D-35392 Giessen, Germany.
authors.forename: Dorothé Jenni
authors.initials: DJ
authors.lastname: Deusing
authors.affiliation: Molecular Nutrition Research, Interdisciplinary Research Center, Justus-Liebig-University of Giessen, Heinrich-Buff-Ring 26-32, D-35392 Giessen, Germany.
authors.forename: Sarah
authors.initials: S
authors.lastname: Winter
authors.affiliation: Plantextrakt GmbH & Co. KG, Dutendorfer Str. 5-7, D-91487 Vestenbergsgreuth, Germany.
authors.forename: Adolf
authors.initials: A
authors.lastname: Kler
authors.affiliation: Plantextrakt GmbH & Co. KG, Dutendorfer Str. 5-7, D-91487 Vestenbergsgreuth, Germany.
authors.forename: Erwin
authors.initials: E
authors.lastname: Kriesl
authors.affiliation: Plantextrakt GmbH & Co. KG, Dutendorfer Str. 5-7, D-91487 Vestenbergsgreuth, Germany.
authors.forename: Bernd
authors.initials: B
authors.lastname: Bonnländer
authors.affiliation: Molecular Nutrition Research, Interdisciplinary Research Center, Justus-Liebig-University of Giessen, Heinrich-Buff-Ring 26-32, D-35392 Giessen, Germany.
authors.forename: Uwe
authors.initials: U
authors.lastname: Wenzel
authors.affiliation: Molecular Nutrition Research, Interdisciplinary Research Center, Justus-Liebig-University of Giessen, Heinrich-Buff-Ring 26-32, D-35392 Giessen, Germany. Electronic address: elena.fitzenberger@ernaehrung.uni-giessen.de.
authors.forename: Elena
authors.initials: E
authors.lastname: Fitzenberger
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000187:drug effects* / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism; D028241:Camellia sinensis / Q000737:chemistry; D002392:Catechin / Q000737:chemistry*; D005947:Glucose / Q000009:adverse effects; D059165:Hormesis / Q000187:drug effects*; D010936:Plant Extracts / Q000494:pharmacology*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D034622:RNA Interference; D037761:Sirtuins / Q000378:metabolism; D013662:Tea / Q000737:chemistry*; D044764:Ubiquitin-Activating Enzymes / Q000378:metabolism
chemical_list: D029742:Caenorhabditis elegans Proteins; D010936:Plant Extracts; D013662:Tea; D002392:Catechin; D046988:Proteasome Endopeptidase Complex; C507014:SIR-2.1 protein, C elegans; D037761:Sirtuins; D044764:Ubiquitin-Activating Enzymes; D005947:Glucose
keywords: Caenorhabditis elegans; Epicatechin (PubChem CID: 72276); Epicatechin gallate (PubChem CID: 107905); Epigallocatechin (PubChem CID: 72277); Epigallocatechin gallate (PubChem CID: 65064); Glucose-induced toxicity; Green tea catechins; Hormesis; Proteasome; SIR-2.1