Pyrroloquinoline quinone increases the expression and activity of Sirt1 and -3 genes in HepG2 cells.
Sirtuin (Sirt) 1 and Sirt 3 are nicotinamide adenine dinucleotide ((+))-dependent protein deacetylases that are important to a number of mitochondrial-related functions; thus, identification of sirtuin activators is important. Herein, we hypothesize that pyrroloquinoline quinone (PQQ) can act as a Sirt1/Sirt3 activator. In HepG2 cell cultures, PQQ increased the expression of Sirt1 and Sirt3 gene, protein, and activity levels (P < .05). We also observed a significant increase in nicotinamide phosphoribosyltransferase gene expression (as early as 18 hours) and increased NAD(+) activity at 24 hours. In addition, targets of Sirt1 and Sirt3 (peroxisome proliferator-activated receptor γ coactivator 1α, nuclear respiratory factor 1 and 2, and mitochondrial transcription factor A) were increased at 48 hours. This is the first report that demonstrates PQQ as an activator of Sirt1 and Sirt3 expression and activity, making it an attractive therapeutic agent for the treatment of metabolic diseases and for healthy aging. Based on our study and the available data in vivo, PQQ has the potential to serve as a therapeutic nutraceutical, when enhancing mitochondrial function.
['Zhang|Jian|J|', 'Meruvu|Sunitha|S|', 'Bedi|Yudhishtar Singh|YS|', 'Chau|Jason|J|', 'Arguelles|Andrix|A|', 'Rucker|Robert|R|', 'Choudhury|Mahua|M|']
D004268:DNA-Binding Proteins D015870:Gene Expression D056945:Hep G2 Cells D006801:Humans D008928:Mitochondria D024101:Mitochondrial Proteins D009243:NAD D054409:Nicotinamide Phosphoribosyltransferase D051266:Nuclear Respiratory Factor 1 D047495:PPAR gamma D045542:PQQ Cofactor D056564:Sirtuin 1 D056566:Sirtuin 3 D014157:Transcription Factors
Pyrroloquinoline quinone Sirtuins Aging Metabolic syndrome Mitochondria Mitochondrial biogenesis regulators