Protective effects of pyrroloquinoline quinine against oxidative stress-induced cellular senescence and inflammation in human renal tubular epithelial cells via Keap1/Nrf2 signaling pathway.
Int Immunopharmacol. 2019 Jul;72:445-453.
Oxidative stress-induced cellular senescence and inflammation are important biological events in diabetic nephropathy (DN). Our recent studies have found that pyrroloquinoline quinine (PQQ) has protective effects against HG-induced oxidative stress damage and apoptosis in HK-2 cells. Nevertheless, whether PPQ has the effect of anti-inflammation and anti-senescence in HK-2 cells remains unclear. Here, we showed that low-dose PPQ treatment (100 nM) downregulates the expression of P16, P21, IL-1β, TNF-α and NF-κB in HG cultured HK-2 cells. A low dose of PPQ also upregulated the protein expression of SOD2, CAT and inhibited the generation of ROS. We also indicated that PPQ affected the activity of Keap1/Nrf2 pathway, increased the nuclear accumulation of Nrf2 and the downstream pathway protein expression of Keap1/Nrf2 signaling pathway (HO-1, NQO-1, GST and GPx-3). When ML385 was added to inhibit the activity of Keap1/Nrf2 signaling pathway, the effects of PPQ on anti-oxidative stress, anti-inflammation and anti-senescence in HK-2 cells under HG condition were weakened. In conclusion, our results suggest that PPQ could modulate HG-induced inflammation and senescence in HK-2 cells via the inhibition of ROS generation and achieves the protective effects through Keap1/Nrf2 pathway and upregulating the expression of its target protein.
PQQ?
Re: PQQ?
Yes, I've been taking it for about 1½ years. I plan to continue as I notice a slight energy boost. It's best to take it early in the day.
I wanted to take something to help mitochondria. I had previously tried nicotinamide riboside, but that gave me chest pain after several months. I haven't had that with PQQ.
Re: PQQ?
Mitochondrial regulation by pyrroloquinoline quinone prevents rotenone-induced neurotoxicity in Parkinson's disease models.
Neurosci Lett. 2018 Nov 20;687:104-110.
Pyrroloquinoline quinone (PQQ), a redox cofactor in the mitochondrial respiratory chain, has been reported to protect SH-SY5Y cells from cytotoxicity induced by rotenone, a mitochondrial complex I inhibitor. In this study, we aimed to investigate the mitochondrial mechanisms involved in the neuroprotection of PQQ both in vitro and in vivo. The cultured human SH-SY5Y neuroblastoma cells were exposed to different concentrations of PQQ after which the cells were treated with rotenone. Electron microscopy images showed that PQQ could prevent the mitochondrial morphology damage. The down-regulation of mitochondrial biogenesis related genes (PGC-1alpha and TFAM) and mitochondrial fission and fusion related genes (Drp1and Mfn2) in rotenone-injured SH-SY5Y cells could be inhibited by PQQ. PQQ could also promote the transposition of Drp1 and Mfn2 from cytosol to mitochondria. In addition, rotenone was injected into the left medial forebrain bundle of SD rats to establish a Parkinson's disease (PD) model in vivo, after which different doses of PQQ or Edaravone were given intraperitoneally once daily for 8 weeks. PQQ could up-regulate the mRNA levels of PGC-1alpha, TFAM, Drp-1 and Mfn2 in the midbrain of PD rats. Our findings indicated that PQQ could prevent mitochondrial dysfunction by promoting mitochondrial biogenesis and regulating mitochondrial fission and fusion, which might contribute to its neuroprotective effect in PD models.
Neurosci Lett. 2018 Nov 20;687:104-110.
Pyrroloquinoline quinone (PQQ), a redox cofactor in the mitochondrial respiratory chain, has been reported to protect SH-SY5Y cells from cytotoxicity induced by rotenone, a mitochondrial complex I inhibitor. In this study, we aimed to investigate the mitochondrial mechanisms involved in the neuroprotection of PQQ both in vitro and in vivo. The cultured human SH-SY5Y neuroblastoma cells were exposed to different concentrations of PQQ after which the cells were treated with rotenone. Electron microscopy images showed that PQQ could prevent the mitochondrial morphology damage. The down-regulation of mitochondrial biogenesis related genes (PGC-1alpha and TFAM) and mitochondrial fission and fusion related genes (Drp1and Mfn2) in rotenone-injured SH-SY5Y cells could be inhibited by PQQ. PQQ could also promote the transposition of Drp1 and Mfn2 from cytosol to mitochondria. In addition, rotenone was injected into the left medial forebrain bundle of SD rats to establish a Parkinson's disease (PD) model in vivo, after which different doses of PQQ or Edaravone were given intraperitoneally once daily for 8 weeks. PQQ could up-regulate the mRNA levels of PGC-1alpha, TFAM, Drp-1 and Mfn2 in the midbrain of PD rats. Our findings indicated that PQQ could prevent mitochondrial dysfunction by promoting mitochondrial biogenesis and regulating mitochondrial fission and fusion, which might contribute to its neuroprotective effect in PD models.
Re: PQQ?
People with MS tend to experience muscle atrophy. Perhaps PQQ can help.
PQQ Ameliorates Skeletal Muscle Atrophy, Mitophagy and Fiber Type Transition Induced by Denervation via Inhibition of the Inflammatory Signaling Pathways
Annals of Translational Medicine, 7 (18), 440
Background: Skeletal muscle atrophy involves and requires widespread changes in skeletal muscle gene expression and signaling pathway, resulting in excessive loss of muscle mass and strength, which is associated with poor prognosis and the decline of life quality in several diseases. However, the treatment of skeletal muscle atrophy remains an unresolved challenge to this day. The aim of the present study was to investigate the influence of pyrroloquinoline quinone (PQQ), a redox-active o-quinone found in various foods and mammalian tissues, on skeletal muscle atrophy, and to explore the underlying molecular mechanism.
Methods: After denervation, mice were injected intraperitoneally with saline plus PQQ (5 mg/kg/d) or saline only for 14 days. The level of inflammatory cytokines in tibialis anterior (TA) muscles was determined by quantitative real-time polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA), and the level of signaling proteins of Janus kinase 2/signal transduction and activator of transcription 3 (Jak2/STAT3), TGF-β1/Smad3, JNK/p38 MAPK, and nuclear factor κB (NF-κB) signaling pathway were detected by Western blot. The skeletal muscle atrophy was evaluated by muscle wet weight ratio and cross-sectional areas (CSAs) of myofibers. The mitophagy was observed through transmission electron microscopy (TEM) analysis, and muscle fiber type transition was analyzed through fast myosin skeletal heavy chain antibody staining.
Results: The proinflammatory cytokines IL-6, IL-1β and TNF-α were largely induced in TA muscles after sciatic nerve transection. PQQ can significantly reverse this phenomenon, as evidenced by the decreased levels of proinflammatory cytokines IL-6, IL-1β and TNF-α. Moreover, PQQ could significantly attenuate the signal activation of Jak2/STAT3, TGF-β1/Smad3, JNK/p38 MAPK, and NF-κB in skeletal muscles after sciatic nerve transection. Furthermore, PQQ alleviated skeletal muscle atrophy, mitigated mitophagy and inhibited slow-to-fast muscle fiber type transition.
Conclusions: These results suggested that PQQ could attenuate denervation-induced skeletal muscle atrophy, mitophagy and fiber type transition through suppressing the Jak2/STAT3, TGF-β1/Smad3, JNK/p38 MAPK, and NF-κB signaling pathways.
Free full text.
PQQ Ameliorates Skeletal Muscle Atrophy, Mitophagy and Fiber Type Transition Induced by Denervation via Inhibition of the Inflammatory Signaling Pathways
Annals of Translational Medicine, 7 (18), 440
Background: Skeletal muscle atrophy involves and requires widespread changes in skeletal muscle gene expression and signaling pathway, resulting in excessive loss of muscle mass and strength, which is associated with poor prognosis and the decline of life quality in several diseases. However, the treatment of skeletal muscle atrophy remains an unresolved challenge to this day. The aim of the present study was to investigate the influence of pyrroloquinoline quinone (PQQ), a redox-active o-quinone found in various foods and mammalian tissues, on skeletal muscle atrophy, and to explore the underlying molecular mechanism.
Methods: After denervation, mice were injected intraperitoneally with saline plus PQQ (5 mg/kg/d) or saline only for 14 days. The level of inflammatory cytokines in tibialis anterior (TA) muscles was determined by quantitative real-time polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA), and the level of signaling proteins of Janus kinase 2/signal transduction and activator of transcription 3 (Jak2/STAT3), TGF-β1/Smad3, JNK/p38 MAPK, and nuclear factor κB (NF-κB) signaling pathway were detected by Western blot. The skeletal muscle atrophy was evaluated by muscle wet weight ratio and cross-sectional areas (CSAs) of myofibers. The mitophagy was observed through transmission electron microscopy (TEM) analysis, and muscle fiber type transition was analyzed through fast myosin skeletal heavy chain antibody staining.
Results: The proinflammatory cytokines IL-6, IL-1β and TNF-α were largely induced in TA muscles after sciatic nerve transection. PQQ can significantly reverse this phenomenon, as evidenced by the decreased levels of proinflammatory cytokines IL-6, IL-1β and TNF-α. Moreover, PQQ could significantly attenuate the signal activation of Jak2/STAT3, TGF-β1/Smad3, JNK/p38 MAPK, and NF-κB in skeletal muscles after sciatic nerve transection. Furthermore, PQQ alleviated skeletal muscle atrophy, mitigated mitophagy and inhibited slow-to-fast muscle fiber type transition.
Conclusions: These results suggested that PQQ could attenuate denervation-induced skeletal muscle atrophy, mitophagy and fiber type transition through suppressing the Jak2/STAT3, TGF-β1/Smad3, JNK/p38 MAPK, and NF-κB signaling pathways.
Free full text.
Re: PQQ?
Thanks. I take R-lipoic acid as well (as Na-R-lipoate, the stabilized form). Lipoic acid was found to be more effective than Ocrevus in preventing brain atrophy in SPMS.
https://www.medicalnewstoday.com/articl ... 5.php?iacp
Re: PQQ?
Pyrroloquinoline-Quinone Is More Than an Antioxidant: A Vitamin-like Accessory Factor Important in Health and Disease Prevention
Biomolecules. 2021 Sep 30;11(10):1441.
Pyrroloquinoline quinone (PQQ) is associated with biological processes such as mitochondriogenesis, reproduction, growth, and aging. In addition, PQQ attenuates clinically relevant dysfunctions (e.g., those associated with ischemia, inflammation and lipotoxicity). PQQ is novel among biofactors that are not currently accepted as vitamins or conditional vitamins. For example, the absence of PQQ in diets produces a response like a vitamin-related deficiency with recovery upon PQQ repletion in a dose-dependent manner. Moreover, potential health benefits, such as improved metabolic flexibility and immuno-and neuroprotection, are associated with PQQ supplementation. Here, we address PQQ's role as an enzymatic cofactor or accessory factor and highlight mechanisms underlying PQQ's actions. We review both large scale and targeted datasets demonstrating that a neonatal or perinatal PQQ deficiency reduces mitochondria content and mitochondrial-related gene expression. Data are reviewed that suggest PQQ's modulation of lactate acid and perhaps other dehydrogenases enhance NAD+-dependent sirtuin activity, along with the sirtuin targets, such as PGC-1α, NRF-1, NRF-2 and TFAM; thus, mediating mitochondrial functions. Taken together, current observations suggest vitamin-like PQQ has strong potential as a potent therapeutic nutraceutical.
Free full text.
Figure 2: PQQ and cellular NAD+. Events elicited by PQQ and NAD+ are highlighted. At the top of the figure, A, niacin-related serum components are depicted that are important in the production of NAD+. Each interacts to generate NAD+ as indicated in the section encircled as B. PQQ plays a role in the process by enhancing the expression of nicotinamide phosphoribosyltransferase (designated as Nampt). Increasing Nampt activity increases NAD+ cellular levels. NAD+ performs two principal functions; first, as a cofactor for dehydrogenases and reductases, such as lactic acid dehydrogenase (LDH), C, and second, as a co-substrate for sirtuin-catalyzed protein deacetylations as noted in D. Likewise, PQQ is a catalytic cofactor for LDH, C. PQQ facilitates the conversion of lactate to pyruvate. In the nucleus, E, NAD+, as a co-substrate for sirtuins, promotes targeted acetylation or deacetylation of proteins involved in cell signaling. Six examples are enumerated: (1) the LKBl/AMP-Kinase-pathway, important in the regulation of rnitochondriogenesis and rates of P-oxidation, (2) Forkhead box 0 transcription factors (FoxO) important to cellular proliferation and survival, (3) transcription factors involving NF-KB and P53 proteins, which regulate multiple aspects of innate and adaptive immune responsiveness, (4) the Janus kinase-signal transducer and activator of transcription JAK-STAT) pathway essential for processes related to hematopoiesis, lactation, and immune responsiveness, (5) peroxisome proliferator-activated receptor-gamma coactivator (PGC-lα), which plays a central role in cellular metabolism and ATP production and (6) the regulation of the mitochondrial transcription factor (TFAM) and other factors essential for mitochondrial genome replication. Finally, in the mitochondria, F. PQQ and NAD+ profoundly impact oxidative metabolism, ROS control, and heat regulation through events controlled by mitochondrial sirtuins and uncoupling proteins, such as UCP2.
8.4. PQQ and Neuroprotection
PQQ is protective in cases and models of brain aging and neurodegeneration, including Parkinson’s disease, stroke, and traumatic brain injury. Perhaps the best of current examples are PQQ’s ability to protect against neuronal agents, such as rotenone [154,155,156,157,158,159,160]. Moreover, the ability of PQQ to protect against neurodegeneration may go beyond mitochondriogenesis, given that PQQ can reduce α—synuclein fibril formation [161]. PQQ also confers resistance to neurocognitive loss in rodent models of stroke and brain injury. Jensen and associates [162] were among the first to use carotid ligation to assess neuroprotective properties following intra peritoneal injection of PQQ. The interruption of blood flow resulted in most of the cortex displaying signs of infarction. Rats without PQQ supplementation had infarctions across −95 percent of cortices compared to −70 percent in rats pretreated with PQQ. In a similar study, Zhang et al. [163] used reversible middle cerebral artery occlusion to simulate interruption of blood circulation to adult rat brains. When PQQ was injected into the jugular vein, either at the same time as occlusion or 3 h after the start of ischemia, markedly improved neurobehavioral scores were observed, along with a reduction in infarct size. Regarding traumatic brain injury, Zhang and associates [155,163,164] assessed spatial memory in rats using the Morris water maze test and demonstrated that PQQ administered intraperitoneally three days before injury improves spatial memory.
In human clinical trials, PQQ was reported to promote cognitive function and improved regional blood flow in older adults [74]. In a randomized placebo-controlled, double-blinded clinical trial, PQQ administered orally (20 mg PQQ/day) to elderly adults resulted in improved cognitive measures. The PQQ dosage was based on a previous animal study showing that PQQ improves spatial memory in rats, as measured by Morris water maze [164].
Biomolecules. 2021 Sep 30;11(10):1441.
Pyrroloquinoline quinone (PQQ) is associated with biological processes such as mitochondriogenesis, reproduction, growth, and aging. In addition, PQQ attenuates clinically relevant dysfunctions (e.g., those associated with ischemia, inflammation and lipotoxicity). PQQ is novel among biofactors that are not currently accepted as vitamins or conditional vitamins. For example, the absence of PQQ in diets produces a response like a vitamin-related deficiency with recovery upon PQQ repletion in a dose-dependent manner. Moreover, potential health benefits, such as improved metabolic flexibility and immuno-and neuroprotection, are associated with PQQ supplementation. Here, we address PQQ's role as an enzymatic cofactor or accessory factor and highlight mechanisms underlying PQQ's actions. We review both large scale and targeted datasets demonstrating that a neonatal or perinatal PQQ deficiency reduces mitochondria content and mitochondrial-related gene expression. Data are reviewed that suggest PQQ's modulation of lactate acid and perhaps other dehydrogenases enhance NAD+-dependent sirtuin activity, along with the sirtuin targets, such as PGC-1α, NRF-1, NRF-2 and TFAM; thus, mediating mitochondrial functions. Taken together, current observations suggest vitamin-like PQQ has strong potential as a potent therapeutic nutraceutical.
Free full text.
Figure 2: PQQ and cellular NAD+. Events elicited by PQQ and NAD+ are highlighted. At the top of the figure, A, niacin-related serum components are depicted that are important in the production of NAD+. Each interacts to generate NAD+ as indicated in the section encircled as B. PQQ plays a role in the process by enhancing the expression of nicotinamide phosphoribosyltransferase (designated as Nampt). Increasing Nampt activity increases NAD+ cellular levels. NAD+ performs two principal functions; first, as a cofactor for dehydrogenases and reductases, such as lactic acid dehydrogenase (LDH), C, and second, as a co-substrate for sirtuin-catalyzed protein deacetylations as noted in D. Likewise, PQQ is a catalytic cofactor for LDH, C. PQQ facilitates the conversion of lactate to pyruvate. In the nucleus, E, NAD+, as a co-substrate for sirtuins, promotes targeted acetylation or deacetylation of proteins involved in cell signaling. Six examples are enumerated: (1) the LKBl/AMP-Kinase-pathway, important in the regulation of rnitochondriogenesis and rates of P-oxidation, (2) Forkhead box 0 transcription factors (FoxO) important to cellular proliferation and survival, (3) transcription factors involving NF-KB and P53 proteins, which regulate multiple aspects of innate and adaptive immune responsiveness, (4) the Janus kinase-signal transducer and activator of transcription JAK-STAT) pathway essential for processes related to hematopoiesis, lactation, and immune responsiveness, (5) peroxisome proliferator-activated receptor-gamma coactivator (PGC-lα), which plays a central role in cellular metabolism and ATP production and (6) the regulation of the mitochondrial transcription factor (TFAM) and other factors essential for mitochondrial genome replication. Finally, in the mitochondria, F. PQQ and NAD+ profoundly impact oxidative metabolism, ROS control, and heat regulation through events controlled by mitochondrial sirtuins and uncoupling proteins, such as UCP2.
8.4. PQQ and Neuroprotection
PQQ is protective in cases and models of brain aging and neurodegeneration, including Parkinson’s disease, stroke, and traumatic brain injury. Perhaps the best of current examples are PQQ’s ability to protect against neuronal agents, such as rotenone [154,155,156,157,158,159,160]. Moreover, the ability of PQQ to protect against neurodegeneration may go beyond mitochondriogenesis, given that PQQ can reduce α—synuclein fibril formation [161]. PQQ also confers resistance to neurocognitive loss in rodent models of stroke and brain injury. Jensen and associates [162] were among the first to use carotid ligation to assess neuroprotective properties following intra peritoneal injection of PQQ. The interruption of blood flow resulted in most of the cortex displaying signs of infarction. Rats without PQQ supplementation had infarctions across −95 percent of cortices compared to −70 percent in rats pretreated with PQQ. In a similar study, Zhang et al. [163] used reversible middle cerebral artery occlusion to simulate interruption of blood circulation to adult rat brains. When PQQ was injected into the jugular vein, either at the same time as occlusion or 3 h after the start of ischemia, markedly improved neurobehavioral scores were observed, along with a reduction in infarct size. Regarding traumatic brain injury, Zhang and associates [155,163,164] assessed spatial memory in rats using the Morris water maze test and demonstrated that PQQ administered intraperitoneally three days before injury improves spatial memory.
In human clinical trials, PQQ was reported to promote cognitive function and improved regional blood flow in older adults [74]. In a randomized placebo-controlled, double-blinded clinical trial, PQQ administered orally (20 mg PQQ/day) to elderly adults resulted in improved cognitive measures. The PQQ dosage was based on a previous animal study showing that PQQ improves spatial memory in rats, as measured by Morris water maze [164].