Cell lines

SK-N-SH cells and HepG2 cells

Preparation Method

SK-N-SH cells and HepG2 cells were incubated with various concentrations of pyrroloquinoline quinone (PQQ) for 24h.

Reaction Conditions

0-500 nM for 24,48, 72 hours

Applications

SK-N-SH and HepG2 cells were incubated with various concentrations of pyrroloquinoline quinone for 24 h. The IC50 values for pyrroloquinoline quinone in SK-N-SH and HepG2 cells were calculated to be 0.17 mM and 0.43 mM, respectively.

Animal models

BALB/c and C57BL/6J

Preparation Method

Pyrroloquinoline quinone concentrations in the basal amino acid diet were determined to be<5 fmol/g diet using a glucose dehydrogenase (GDH) enzyme assay for pyrroloquinoline quinone quantitation. Pyrroloquinoline quinone was added to diets at 2 mg/kg (∼6 nmol/g) diet. In typical protocols, virgin females were adapted to the basal (devoid of Pyrroloquinoline quinone) diet for ≥2 wk. Half of the females were then switched to a diet supplemented with 2 mg PQQ/kg diet, and the other half were fed the basal diet. Both groups of females (F0 generation) were then bred; the resulting pups (F1 generation) were weaned at 28 d of age and fed the same diet as their dams until used in selected assays.

Dosage form

2 mg/kg (∼6 nmol/g) diet, more than 2 weeks

Applications

The amount of mitochondria in liver from pyrroloquinoline quinone -deprived mice was less than that from Pyrroloquinoline quinone -supplemented mice based on cross-sectional area estimates

Pyrroloquinoline quinone was reported to be a new mammalian lactate dehydrogenase (LDH) coenzyme^[1]. Pyrroloquinoline quinone has diverse effects including an antioxidant effect, a cell growth-promoting effect, and a stimulatory effect on mitochondriogensis^{[2,3,4,5,6,7]}

Pyrroloquinoline quinone protected against oxidative damage caused by H₂O₂, because it has many reducing sites. It was suggested that HepG2 cells require more pyrroloquinoline quinone due to the greater damage caused by hydrogen peroxide than do SK-N-SH cells^[8]. Pyrroloquinoline quinone showed protect effect on 6-OHDA using human neuroblastoma SH-SY5Y cells at 15 μM^[9].

Pyrroloquinoline quinone can serve as a growth factor in BALB/c mice [10]. The lower values for RQ in PQQ-deficient mice compared with PQQ-supplemented mice, as a sign of compromised mitochondrial function and inefficient carbohydrate utilization^[11].

References:
[1]. Akagawa M, Minematsu K, Shibata T, et al. Identification of lactate dehydrogenase as a mammalian pyrroloquinoline quinone (PQQ)-binding protein[J]. Scientific reports, 2016, 6(1): 1-19.
[2]. He K, Nukada H, Urakami T, et al. Antioxidant and pro-oxidant properties of pyrroloquinoline quinone (PQQ): implications for its function in biological systems[J]. Biochemical pharmacology, 2003, 65(1): 67-74.
[3]. Nunome K, Miyazaki S, Nakano M, et al. Pyrroloquinoline quinone prevents oxidative stress-induced neuronal death probably through changes in oxidative status of DJ-1[J]. Biological and Pharmaceutical Bulletin, 2008, 31(7): 1321-1326.
[4]. Zhang Y, Feustel P J, Kimelberg H K. Neuroprotection by pyrroloquinoline quinone (PQQ) in reversible middle cerebral artery occlusion in the adult rat[J]. Brain research, 2006, 1094(1): 200-206.
[5]. Yamaguchi K, Sasano A, Urakami T, et al. Stimulation of nerve growth factor production by pyrroloquinoline quinone and its derivatives in vitro and in vivo[J]. Bioscience, biotechnology, and biochemistry, 1993, 57(7): 1231-1233.
[6]. Stites T, Storms D, Bauerly K, et al. Pyrroloquinoline quinone modulates mitochondrial quantity and function in mice[J]. The Journal of nutrition, 2006, 136(2): 390-396.
[7]. Chowanadisai W, Bauerly K A, Tchaparian E, et al. Pyrroloquinoline quinone stimulates mitochondrial biogenesis through cAMP response element-binding protein phosphorylation and increased PGC-1α expression[J]. Journal of Biological Chemistry, 2010, 285(1): 142-152.
[8]. Yamada Y, Nishii K, Kuwata K, et al. Effects of pyrroloquinoline quinone and imidazole pyrroloquinoline on biological activities and neural functions[J]. Heliyon, 2020, 6(1): e03240.
[9]. Hara H, Hiramatsu H, Adachi T. Pyrroloquinoline quinone is a potent neuroprotective nutrient against 6-hydroxydopamine-induced neurotoxicity[J]. Neurochemical research, 2007, 32(3): 489-495.
[10]. Naito Y, Kumazawa T, Kino I, et al. Effects of pyrroloquinoline quinone (PQQ) and PQQ-oxazole on DNA synthesis of cultured human fibroblasts[J]. Life sciences, 1993, 52(24): 1909-1915.
[11]. Stites T, Storms D, Bauerly K, et al. Pyrroloquinoline quinone modulates mitochondrial quantity and function in mice[J]. The Journal of nutrition, 2006, 136(2): 390-396.