Biological effects of pyrroloquinoline quinone on liver damage in Bmi-1 knockout mice

Abstract

Abstract. Pyrroloquinoline quinone (PQQ) has been demonstrated to function as an antioxidant by scavenging free radicals and subsequently protecting the mitochondria from oxidative stress-induced damage. The aim of the present study was to investigate whether PQQ is able to rescue premature senescence in the liver, induced by the deletion of B cell-specific Moloney MLV insertion site-1 (Bmi-1), by inhibiting oxidative stress. In vivo, the mice were allocated into three groups that underwent the following treatment protocols. WT mice received a normal diet, while BKO mice also received a normal diet. An additional group of BKO mice were fed a PQQ-supplemented diet (BKO + PQQ; 4 mg PQQ/kg in the normal diet). The results indicated that PQQ partially rescued the liver damage induced by the deletion of Bmi-1. PQQ was demonstrated to exhibit these therapeutic effects on liver damage through multiple aspects, including the promotion of proliferation, antiapoptotic effects, the inhibition of senescence, the upregulation of antioxidant ability, the downregulation of cell cycle protein expression, the scavenging of reactive oxygen species and the reduction of DNA damage. The results of these experiments indicated that treatment of BKO mice with a moderate dose of PQQ significantly protected the liver from deleterious effects by inhibiting oxidative stress and participating in DNA damage repair. Therefore, PQQ has great potential as a therapeutic agent against oxidative stress during liver damage. IntroductionThe liver is a unique organ that is usually silent under physiological conditions; however, the organ exhibits regenerative properties following damage and/or parenchymal loss (1). In previous years, hepatic disease and the associated morbidity rates have increased year by year, with the condition becoming a major global health care problem (2). A previous study demonstrated that reactive oxygen species (ROS) may be a cause of liver damage, which is characterized by a progression from steatosis to chronic hepatitis, cirrhosis and hepatocellular carcinoma (3). Although studies have attempted to identify efficient liver therapeutics from herbal origins, a number of the potential candidates have not been well characterized and require further investigation (4).Over 50 years ago, Harman proposed the free radical or oxidative stress theory of aging (5). The author hypothesized that free radicals and/or ROS are produced endogenously from normal cellular metabolic processes. In this theory, an imbalance between ROS and antioxidants can lead to oxidative stress, which subsequently damages various macromolecules. An increasing body of evidence has demonstrated that an increased production of ROS plays an important role in the development of various age-associated diseases (6).B cell-specific Moloney MLV insertion site-1 (Bmi-1) belongs to the Polycomb group of genes, which are transcriptional repressors that are essential for the maintenance of appropriate gene expression patterns during development (7). The premature deletio...

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BMI1 promotes steroidogenesis through maintaining redox homeostasis in mouse MLTC-1 and primary Leydig cells

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