Pyrroloquinoline quinone increases the expression and activity of Sirt1 and -3 genes in HepG2 cells

Abstract

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.

Mitochondrial Sirtuin 3: New emerging biological function and therapeutic target

“…Moreover, in a mouse model of sulfur mustard-induced hepatic injury, this natural product exerts its hepatoprotective effects via SIRT3 179 . Pyrroloquinoline quinone, another natural product, can improve liver metabolic diseases through increasing the expression of SIRT3 180 .…”

Nuclear Magnetic Resonance Structure and Binding Studies of PqqD, a Chaperone Required in the Biosynthesis of the Bacterial Dehydrogenase Cofactor Pyrroloquinoline Quinone

“…23–26 The specific mechanism(s) by which PQQ alters reproductive success are currently unknown, although data are emerging that PQQ promotes mitochondrial metabolism. 27–33 As an antioxidant, PQQ can undergo approximately 20,000 redox cycles, making it, on a molar basis, 100-times more efficient than ascorbic acid as a cellular redox molecule. 34–36 …”

1H, 13C, and 15N resonance assignments and secondary structure information for Methylobacterium extorquens PqqD and the complex of PqqD with PqqA

“…It is a tricyclic, redox active o-quinone that is not formed by direct post-translational modification of active site residues, but instead is synthesized by way of a RiPP pathway (Goodwin 1998; Anthony 2001; Latham et al 2015). PQQ is a significant antioxidant, and when present supports mitochondrial biogenesis and function in a wide range of organisms (Bauerly et al 2011; Bauerly et al 2006; Chowanadisai et al 2010; Harris et al 2013; Stites et al 2006; Singh et al 2015; Zhang et al 2015). Additionally, PQQ demonstrates probiotic properties in mammals; studies with rats and mice have demonstrated decreased growth, reduced immune response, and declining reproductive success when subjects were deprived of PQQ in their diets (Kasahara and Kato 2003; Killgore et al 1989; Steinberg et al 2003; Steinberg et al 1994).…”