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.
Department of Pharmaceutical Sciences, Irma Lerma Rangel College of Pharmacy, Texas A&M Health Science Center, Kingsville, TX, USA.
Jian
J
Zhang
Department of Pharmaceutical Sciences, Irma Lerma Rangel College of Pharmacy, Texas A&M Health Science Center, Kingsville, TX, USA.
Sunitha
S
Meruvu
Department of Pharmaceutical Sciences, Irma Lerma Rangel College of Pharmacy, Texas A&M Health Science Center, Kingsville, TX, USA.
Yudhishtar Singh
YS
Bedi
Department of Pharmaceutical Sciences, Irma Lerma Rangel College of Pharmacy, Texas A&M Health Science Center, Kingsville, TX, USA.
Jason
J
Chau
Department of Pharmaceutical Sciences, Irma Lerma Rangel College of Pharmacy, Texas A&M Health Science Center, Kingsville, TX, USA.
Andrix
A
Arguelles
Department of Nutrition, University of California, Davis, CA, USA.
Robert
R
Rucker
Department of Pharmaceutical Sciences, Irma Lerma Rangel College of Pharmacy, Texas A&M Health Science Center, Kingsville, TX, USA. Electronic address: mchoudhury@pharmacy.tamhsc.edu.
Mahua
M
Choudhury
D004268:DNA-Binding Proteins / Q000378:metabolism; D015870:Gene Expression; D056945:Hep G2 Cells; D006801:Humans; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000378:metabolism; D009243:NAD / Q000378:metabolism; D054409:Nicotinamide Phosphoribosyltransferase / Q000378:metabolism; D051266:Nuclear Respiratory Factor 1 / Q000378:metabolism; D047495:PPAR gamma / Q000378:metabolism; D045542:PQQ Cofactor / Q000494:pharmacology*; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism*; D056566:Sirtuin 3 / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism
D004268:DNA-Binding Proteins; D024101:Mitochondrial Proteins; D051266:Nuclear Respiratory Factor 1; D047495:PPAR gamma; D014157:Transcription Factors; C422562:mitochondrial transcription factor A; C111264:peroxisome-proliferator-activated receptor-gamma coactivator-1; D009243:NAD; D045542:PQQ Cofactor; D054409:Nicotinamide Phosphoribosyltransferase; D056564:Sirtuin 1; D056566:Sirtuin 3
Aging; Metabolic syndrome; Mitochondria; Mitochondrial biogenesis regulators; Pyrroloquinoline quinone; Sirtuins