Antiviral Effects of Pyrroloquinoline Quinone through Redox Catalysis To Prevent Coronavirus Infection
Ontology highlight
ABSTRACT:
SUBMITTER:
PROVIDER: S-EPMC10688161 | biostudies-literature | 2023 Nov
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Pyrroloquinoline quinone (PQQ) is a peptide-derived redox cofactor produced by prokaryotes that also plays beneficial roles in organisms from other kingdoms. We review recent developments on the pathway of PQQ biogenesis, focusing on the mechanisms of PqqE, PqqF/G, and PqqB. These advances may shed light on other, uncharacterized biosynthetic pathways.
| S-EPMC7736144 | biostudies-literature
Project description:BackgroundMyocardial mitochondrial dysfunction is the leading cause of chronic heart failure (CHF). Increased reactive oxygen species (ROS) levels, disruption of mitochondrial biogenesis and mitochondrial Ca2+([Ca2+]m) homeostasis and reduction of the mitochondrial membrane potential (ΔΨm) cause myocardial mitochondrial dysfunction. Therefore, treating CHF by targeting mitochondrial function is a focus of current research. For the first time, this study investigated the effects of the strong antioxidant pyrroloquinoline quinone (PQQ) on mitochondrial function in a cardiac pressure overload model, and the mechanism by which PQQ regulates [Ca2+]m homeostasis was explored in depth.MethodsAfter transaortic constriction (TAC), normal saline and PQQ (0.4, 2 and 10 mg/kg) were administered intragastrically to Sprague Dawley (SD) rats for 12 weeks. In vitro, neonatal rat left ventricle myocytes (NRVMs) were pretreated with 200 nm angiotensin II (Ang II) with or without PQQ (1, 10 and 100 μM). Rat heart remodelling was verified by assessment of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) levels (qRT-PCR), cell surface area (wheat germ agglutinin (WGA) staining in vivo and α-actin in vitro) and echocardiography. Myocardial mitochondrial morphology was assessed by transmission electron microscopy. Western blotting was used to assess mitochondrial biogenesis [peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) and transcription factor A, mitochondrial (TFAM)]. The ΔΨm was determined by tetraethyl benzimidazolyl carbocyanine iodide (JC-1) staining and flow cytometry, and ROS levels were measured by dichloro-dihydro-fluorescein diacetate (DCFH-DA) and MitoSOX Red staining. [Ca2+]m was measured by isolating rat mitochondria, and mitochondrial Ca2+ channel proteins [the mitochondrial Na+/Ca2+ exchanger (NCLX) and mitochondrial Ca2+ uniporter (MCU)] were detected by Western blot.ResultsIn vivo and in vitro, PQQ pretreatment improved pressure overload-induced cardiac remodelling and cell hypertrophy, thus preventing the occurrence of CHF. PQQ also prevented mitochondrial morphology damage and reduced the PGC-1α and TFAM downregulation caused by TAC or Ang II. In addition, in NRVMs treated with Ang II + PQQ, PQQ regulated ROS levels and increased the ΔΨm. PQQ also regulated [Ca2+]m homeostasis and prohibited [Ca2+]m overloading by increasing NCLX expression.ConclusionsThese results show that PQQ can prevent [Ca2+]m overload by increasing NCLX expression and thereby reducing ROS production and protecting the ΔΨm. At the same time, PQQ can increase PGC-1α and TFAM expression to regulate mitochondrial biogenesis. These factors can prevent mitochondrial dysfunction, thereby reducing cardiac damage caused by pressure overload and preventing the occurrence of CHF.
| S-EPMC7369269 | biostudies-literature
Project description:BackgroundFolates (Vitamin B9) are critical for normal neurodevelopment and function, with transport mediated by three major pathways: folate receptor alpha (FRα), proton-coupled folate transporter (PCFT), and reduced folate carrier (RFC). Cerebral folate uptake primarily occurs at the blood-cerebrospinal fluid barrier (BCSFB) through concerted actions of FRα and PCFT, with impaired folate transport resulting in the neurological disorder cerebral folate deficiency (CFD). Increasing evidence suggests that disorders associated with CFD also present with neuroinflammation, oxidative stress, and mitochondrial dysfunction, however the role of brain folate deficiency in inducing these abnormalities is not well-understood. Our laboratory has identified the upregulation of RFC by nuclear respiratory factor 1 (NRF-1) at the blood-brain barrier (BBB) once indirectly activated by the natural compound pyrroloquinoline quinone (PQQ). PQQ is also of interest due to its anti-inflammatory, antioxidant, and mitochondrial biogenesis effects. In this study, we examined the effects of folate deficiency and PQQ treatment on inflammatory and oxidative stress responses, and changes in mitochondrial function.MethodsPrimary cultures of mouse mixed glial cells exposed to folate-deficient (FD) conditions and treated with PQQ were analyzed for changes in gene expression of the folate transporters, inflammatory markers, oxidative stress markers, and mitochondrial DNA (mtDNA) content through qPCR analysis. Changes in cellular reactive oxygen species (ROS) levels were analyzed in vitro through a DCFDA assay. Wildtype (C57BL6/N) mice exposed to FD (0 mg/kg folate), or control (2 mg/kg folate) diets underwent a 10-day (20 mg/kg/day) PQQ treatment regimen and brain tissues were collected and analyzed.ResultsFolate deficiency resulted in increased expression of inflammatory and oxidative stress markers in vitro and in vivo, with increased cellular ROS levels observed in mixed glial cells as well as a reduction of mitochondrial DNA (mtDNA) content observed in FD mixed glial cells. PQQ treatment was able to reverse these changes, while increasing RFC expression through activation of the PGC-1α/NRF-1 signaling pathway.ConclusionThese results demonstrate the effects of brain folate deficiency, which may contribute to the neurological deficits commonly seen in disorders of CFD. PQQ may represent a novel treatment strategy for disorders associated with CFD, as it can increase folate uptake, while in parallel reversing many abnormalities that arise with brain folate deficiency.
| S-EPMC10659058 | biostudies-literature
Project description:Pulmonary fibrosis is a lung disorder affecting the lungs that involves the overexpressed extracellular matrix, scarring and stiffening of tissue. The repair of lung tissue after injury relies heavily on Type II alveolar epithelial cells (AEII), and repeated damage to these cells is a crucial factor in the development of pulmonary fibrosis. Studies have demonstrated that chronic exposure to PM2.5, a form of air pollution, leads to an increase in the incidence and severity of pulmonary fibrosis by stimulation of epithelial-mesenchymal transition (EMT) in lung epithelial cells. Pyrroloquinoline quinone (PQQ) is a bioactive compound found naturally that exhibits potent anti-inflammatory and anti-oxidative properties. The mechanism by which PQQ prevents pulmonary fibrosis caused by exposure to PM2.5 through EMT has not been thoroughly discussed until now. In the current study, we discovered that PQQ successfully prevented PM2.5-induced pulmonary fibrosis by targeting EMT. The results indicated that PQQ was able to inhibit the expression of type I collagen, a well-known fibrosis marker, in AEII cells subjected to long-term PM2.5 exposure. We also found the alterations of cellular structure and EMT marker expression in AEII cells with PM2.5 incubation, which were reduced by PQQ treatment. Furthermore, prolonged exposure to PM2.5 considerably reduced cell migratory ability, but PQQ treatment helped in reducing it. In vivo animal experiments indicated that PQQ could reduce EMT markers and enhance pulmonary function. Overall, these results imply that PQQ might be useful in clinical settings to prevent pulmonary fibrosis.
| S-EPMC11015390 | biostudies-literature
Project description:Liver fibrosis represents the consequences of a sustained wound healing response to chronic liver injuries, and its progression toward cirrhosis is the major cause of liver-related morbidity and mortality worldwide. However, anti-fibrotic treatment remains an unconquered area for drug development. Accumulating evidence indicate that oxidative stress plays a critical role in liver fibrogenesis. In this study, we found that PQQ, a natural anti-oxidant present in a wide variety of human foods, exerted potent anti-fibrotic and ROS-scavenging activity in Balb/C mouse models of liver fibrosis. The antioxidant activity of PQQ was involved in the modulation of multiple steps during liver fibrogenesis, including chronic liver injury, hepatic inflammation, as well as activation of hepatic stellate cells and production of extracellular matrix. PQQ also suppressed the up-regulation of RACK1 in activated HSCs in vivo and in vitro. Our data suggest that PQQ suppresses oxidative stress and liver fibrogenesis in mice, and provide rationale for the clinical application of PQQ in the prevention and treatment of liver fibrosis.
| S-EPMC4379100 | biostudies-literature
Project description:Oxidation reactions are fundamental transformations in organic synthesis and chemical industry. With oxygen or air as terminal oxidant, aerobic oxidation catalysis provides the most sustainable and economic oxidation processes. Most aerobic oxidation catalysis employs redox metal as its active center. While nature provides non-redox metal strategy as in pyrroloquinoline quinone (PQQ)-dependent methanol dehydrogenases (MDH), such an effective chemical version is unknown. Inspired by the recently discovered rare earth metal-dependent enzyme Ln-MDH, here we show that an open-shell semi-quinone anionic radical species in complexing with lanthanum could serve as a very efficient aerobic oxidation catalyst under ambient conditions. In this catalyst, the lanthanum(III) ion serves only as a Lewis acid promoter and the redox process occurs exclusively on the semiquinone ligand. The catalysis is initiated by 1e--reduction of lanthanum-activated ortho-quinone to a semiquinone-lanthanum complex La(SQ-.)2, which undergoes a coupled O-H/C-H (PCHT: proton coupled hydride transfer) dehydrogenation for aerobic oxidation of alcohols with up to 330 h-1 TOF.
| S-EPMC8776754 | biostudies-literature
Project description:Endophytic bacteria are a group of microorganisms that can intercellularly colonize plant hosts without causing apparent damage or disease. Our previous works found that a pyrroloquinoline quinone (PQQ)-producing endophyte could promote plant growth and systemic tolerance. To demonstrate this PQQ-producing endophyte's beneficial role in plants, a set of five PQQ synthesis genes from Gluconobacter oxydans was introduced into both Escherichia coli JM109 and Bacillus subtilis RM125, a BsuM-deficient mutant of laboratory strain B. subtilis 168. Interestingly, both strains harboring the PQQ synthesis genes exhibited significantly higher optimal optical density than control strains. In a carbon flux analysis, both strains showed a noticeable increase in their citric acid, alpha-ketoglutaric acid, and succinic acid levels. Conversely, in E. coli, pyruvic acid, malic acid, and fumaric acid levels decreased. These results suggest that PQQ impacts various host species differently. Furthermore, the presence of PQQ in fermentation broth was also confirmed in the RM125 PQQ synthesis recombinant strain. Subsequent experiments by inoculating those Bacillus strains revealed that the laboratory host strain could function as an endophyte, and the PQQ transgenic strain could further promote the growth of Arabidopsis thaliana and increase the number of siliques. These findings confirm PQQ's vital role in endophyte-mediated plant growth promotion and also suggest the potential of B. subtilis transformed with PQQ genes as an engineered endophyte for studying PQQ's biological functions in plants. This research is a step forward in understanding how specific substances can beneficially influence plant growth and systemic tolerance through endophytic mechanisms.
| S-EPMC11858353 | biostudies-literature
Project description:We investigated whether the oxidoreductase cofactor pyrroloquinoline quinone (PQQ) prevents noise-induced and age-related hearing loss (NIHL and ARHL) in mice. To assess NIHL, 8 week-old mice with and without PQQ administration were exposed to noise for 4 h. PQQ was orally administered for one week before and after noise exposure and subcutaneously once before noise exposure. For ARHL evaluation, mice were given drinking water with or without PQQ starting at 2 months of age. In the NIHL model, PQQ-treated mice had auditory brainstem response (ABR) thresholds of significantly reduced elevation at 8 kHz, a significantly increased number of hair cells at the basal turn, and significantly better maintained synapses beneath the inner hair cells compared to controls. In the ARHL model, PQQ significantly attenuated the age-related increase in ABR thresholds at 8 and 32 kHz at 10 months of age compared to controls. In addition, the hair cells, spiral ganglion cells, ribbon synapses, stria vascularis and nerve fibers were all significantly better maintained in PQQ-treated animals compared to controls at 10 months of age. These physiological and histological results demonstrate that PQQ protects the auditory system from NIHL and ARHL in mice.
| S-EPMC9508078 | biostudies-literature
Project description:Sperm motility is an important factor in the migration of sperm from the uterus to the oviduct. During sperm preservation in vitro, sperm generates excessive ROS that damages its function. This study aims to investigate whether the addition of pyrroloquinoline quinone (PQQ) to the diluted medium could improve chilled ram sperm quality, and then elucidates the mechanism. Ram semen was diluted with Tris-citric acid-glucose (TCG) medium containing different doses of PQQ (0 nM, 10 nM, 100 nM, 1000 nM, 10,000 nM), and stored at 4 °C. Sperm motility patterns, plasma membrane integrity, acrosome integrity, mitochondrial membrane potential, reactive oxygen species (ROS) levels, malondialdehyde (MDA) levels, superoxide dismutase (SOD) activity, and ATP levels were measured after preservation. Furthermore, the expressions of NADH dehydrogenase 1 (MT-ND1) and NADH dehydrogenase 6 (MT-ND6) in sperm were also detected by western blotting. In addition, sperm capacitation and the ability of sperm to bind to the zona pellucina were also evaluated. It was observed that the addition of PQQ significantly (p < 0.05) improved ram sperm motility, membrane integrity, and acrosome integrity during preservation. The percentage of sperm with high mitochondrial membrane potential in the PQQ treatment group was much higher than that in the control. In addition, supplementation of PQQ also decreased the sperm MDA and ROS levels, while increasing ATP levels. Interestingly, the levels of MT-ND1 and MT-ND6 protein in sperm treated with PQQ were also higher than that of the control. Furthermore, the addition of 100 nM PQQ to the medium decreased ROS damage in MT-ND1 and MT-ND6 proteins. The addition of 100 nM PQQ significantly (p < 0.05) increased protein tyrosine phosphorylation in ram sperm after induced capacitation. Furthermore, the value of the sperm-zona pellucida binding capacity in the 100 nM PQQ treatment group was also much higher than that of the control. Overall, during chilled ram- sperm preservation, PQQ protected ram sperm quality by quenching the ROS levels to reduce ROS damage and maintain sperm mitochondrial function, and preserved the sperm's high ability of fertilization.
| S-EPMC10812569 | biostudies-literature
Project description:BackgroundThe biosynthesis pathway of Pyrroloquinoline quinone, a bacterial redox active cofactor for numerous alcohol and aldose dehydrogenases, is largely unknown, but it is proven that at least six genes in Klebsiella pneumoniae (PqqA-F) are required, all of which are located in the PQQ-operon.ResultsNew structural data of some PQQ biosynthesis proteins and their homologues provide new insights and functional assignments of the proteins in the pathway. Based on sequence analysis and homology models we propose the role and catalytic function for each enzyme involved in this intriguing biosynthesis pathway.ConclusionPQQ is derived from the two amino acids glutamate and tyrosine encoded in the precursor peptide PqqA. Five reactions are necessary to form this quinone cofactor. The PqqA peptide is recognised by PqqE, which links the C9 and C9a, afterwards it is accepted by PqqF which cuts out the linked amino acids. The next reaction (Schiff base) is spontaneous, the following dioxygenation is catalysed by an unknown enzyme. The last cyclization and oxidation steps are catalysed by PqqC. Taken together the known facts of the different proteins we assign a putative function to all six proteins in PQQ biosynthesis pathway.
| S-EPMC2294125 | biostudies-literature