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

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• 作者：Jian Zhang^a ; Sunitha Meruvu^a ; Yudhishtar Singh Bedi^a ; Jason Chau^a ; Andrix Arguelles^a ; Robert Rucker^b ; Mahua Choudhury^a ; ^{mchoudhury@pharmacy.tamhsc.edu" class="auth_mail" title="E-mail the corresponding author} ;
• 关键词：Sirtuins ; Pyrroloquinoline quinone ; Metabolic syndrome ; Mitochondria ; Aging ; Mitochondrial biogenesis regulators
• 刊名：Nutrition Research
• 出版年：2015
• 出版时间：September 2015
• 年：2015
• 卷：35
• 期：9
• 页码：844-849
• 全文大小：589 K

文摘

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 纬 coactivator 1伪, 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.