title: Resveratrol affects undifferentiated and differentiated PC12 cells differently, particularly with respect to possible differences in mitochondrial and autophagic functions.
abstract: Since resveratrol is considered to exert a unique dual effect, protective for normal cells but toxic to tumor cells, its action on undifferentiated (original) and differentiated PC12 cells was analyzed, because undifferentiated cells are tumorigenic and differentiated ones are neuronal in nature. Compared to resveratrol-untreated cells in both undifferentiated and differentiated cell groups, cells treated with different doses of resveratrol, at dosages of 1, 10 and 100 μM, showed the following alterations. Dying/dead cells were significantly increased in a dose-dependent manner in undifferentiated cells, but they were unchanged at doses of up to 10 μM resveratrol in differentiated cells. In living cells, neurites were short in undifferentiated cells, but drastically elongated with an increased number in differentiated cells. The expression of SIRT1 was drastically reduced in undifferentiated cells, but stable in differentiated cells. SIRT3 was significantly enhanced in a dose-dependent manner at resveratrol doses of up to 10 μM in both cells, with reduction and more enhanced at a dosage of 100 μM in undifferentiated and differentiated cells, respectively. Mitochondrial number and ATP synthase β subunit expression was unaltered at doses of up to 10 μM and were significantly reduced at doses of 100 μM in undifferentiated cells, but they were significantly increased in a dose-dependent manner, with a slight reduction in the ATP synthase at doses of 100 μM, in differentiated cells. In a dose-dependent manner, the number of autophagosomes and the LC3-II/LC3-I ratio were significantly less in undifferentiated cells and greater in differentiated cells. Also, in a dose-dependent manner, the expression of phosphorylated AMP-activated kinase (AMPK) was significantly less in undifferentiated cells and greater in differentiated cells. Resveratrol-induced AMPK suppression and activation, possibly through the modulation of SIRT protein activity, may thus be related to the inhibition and promotion of mitochondrial and autophagic functions, leading to cell death and survival in undifferentiated and differentiated cells, respectively.
authors.affiliation: Laboratory of Cell Biology, College of Nutrition, Koshien University, Takarazuka, Hyogo 665-0006, Japan.
authors.forename: Naoya
authors.initials: N
authors.lastname: Hayakawa
authors.forename: Motoko
authors.initials: M
authors.lastname: Shiozaki
authors.forename: Masahiro
authors.initials: M
authors.lastname: Shibata
authors.forename: Masato
authors.initials: M
authors.lastname: Koike
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Uchiyama
authors.forename: Nariaki
authors.initials: N
authors.lastname: Matsuura
authors.forename: Takahiro
authors.initials: T
authors.lastname: Gotow
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001343:Autophagy / Q000187:drug effects*; D002454:Cell Differentiation; D005786:Gene Expression Regulation / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D025261:Mitochondrial Proton-Translocating ATPases / Q000235:genetics / Q000378:metabolism; D016501:Neurites / Q000187:drug effects; D016716:PC12 Cells; D051381:Rats; D000077185:Resveratrol; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism; D013267:Stilbenes / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D000099156:Superoxide Dismutase 2
chemical_list: D055372:AMP-Activated Protein Kinases; D025261:Mitochondrial Proton-Translocating ATPases; D000077185:Resveratrol; D056564:Sirtuin 1; D013267:Stilbenes; D013482:Superoxide Dismutase; D000099156:Superoxide Dismutase 2; C488368:Sirt1 protein, rat; C497342:ATP synthase beta subunit, rat