ABSTRACT
Trichomoniasis is caused by a sexually transmitted flagellate protozoan parasite Trichomonas vaginalis. T. vaginalis-derived secretory products (TvSP) contain lipid mediators such as leukotriene B4 (LTB4) and various cysteinyl leukotrienes (CysLTs) which included LTC4, LTD4, and LTE4. However, the signaling mechanisms by which T. vaginalis-induced CysLTs stimulate interleukin (IL)-8 production in human mast cells remain unclear. In this study, we investigated these mechanisms in human mast cells (HMC-1). Stimulation with TvSP resulted in increased intracellular reactive oxygen species (ROS) generation and NADPH oxidase 2 (NOX2) activation compared to unstimulated cells. Pre-treatment with NOX2 inhibitors such as diphenyleneiodonium chloride (DPI) or apocynin significantly reduced ROS production in TvSP-stimulated HMC-1 cells. Additionally, TvSP stimulation increased NOX2 protein expression and the translocation of p47phox from the cytosol to the membrane. Pretreatment of HMC-1 cells with PI3K or PKC inhibitors reduced TvSP-induced p47phox translocation and ROS generation. Furthermore, NOX2 inhibitors or NOX2 siRNA prevented CREB phosphorylation and IL-8 gene expression or protein secretion induced by TvSP. Pretreatment with a CysLTR antagonist significantly inhibited TvSP-induced ROS production, CREB phosphorylation, and IL-8 production. These results indicate that CysLT-mediated activation of NOX2 plays a crucial role in ROS-dependent IL-8 production in human mast cells stimulated by T. vaginalis-secreted CysLTs. These findings enhance our understanding of the inflammatory response in trichomoniasis and may inform the development of targeted therapies to mitigate this response.
Subject(s)
Interleukin-8 , Mast Cells , NADPH Oxidase 2 , Reactive Oxygen Species , Receptors, Leukotriene , Trichomonas vaginalis , Humans , Trichomonas vaginalis/drug effects , Trichomonas vaginalis/metabolism , Interleukin-8/metabolism , Interleukin-8/genetics , Reactive Oxygen Species/metabolism , NADPH Oxidase 2/metabolism , NADPH Oxidase 2/genetics , Mast Cells/metabolism , Mast Cells/drug effects , Mast Cells/parasitology , Mast Cells/immunology , Cell Line , Receptors, Leukotriene/metabolism , Receptors, Leukotriene/genetics , NADPH Oxidases/metabolism , Signal Transduction/drug effects , Leukotrienes/metabolismABSTRACT
Corneal neovascularization (CoNV) is the second leading cause of visual impairment worldwide, and current drugs have certain limitations. Inflammatory response is the core pathological process of CoNV. Neutrophil extracellular traps (NETs) are generated after neutrophil activation, which promotes neovascularization. Prior studies demonstrated that bone morphogenetic protein 4 (BMP4) could significantly reduce inflammation and CoNV formation, its exact molecular mechanism remains unclear. Therefore, we stimulated human peripheral blood neutrophils with phorbol myristate acetate (PMA) or deoxyribonuclease I (DNase I) to induce or inhibit NETs formation. By using corneal sutures and subconjunctival injections of NETs or DNase I, rat CoNV models were established. Compared with the suture group, NETs formation and inflammatory cell infiltration in the corneal stroma were significantly increased, corneal edema was aggravated, and the length, area and diameter of CoNV were significantly enhanced in the NETs group. Furthermore, by curetting the corneal epithelial apical junctional complexes (AJCs), a crucial component in preserving the function of the corneal epithelial barrier, we discovered that the damage of AJCs had a significant role in inducing CoNV formation. NETs could induce CoNV formation by injuring corneal epithelial AJCs. Finally, by comparing the aforementioned indicators after the intervention of BMP4, BMP4 inhibitor Noggin and NADPH oxidase (NOX) inhibitor, we finally demonstrated that BMP4 could inhibit NETs-induced inflammation and corneal epithelial AJC injury, repair corneal epithelial barrier function and eventually inhibit CoNV formation by blocking NOX-2-dependent NETs formation.
ABSTRACT
The vitamin D receptor (VDR) is associated with antioxidative and anti-inflammatory effects and modulation of the renin-angiotensin-aldosterone system. This study evaluated whether VDR agonist paricalcitol protects renal ischemia-reperfusion (IR) induced tubular injury in rats by evaluating: 1) ATP-dependent tubular Na+ transport; 2) renal redox signaling; 3) renal content of proinflammatory cytokines TNF-α and IL-6; and 4) renal content of renin and angiotensin II receptor type 1 (AT1R). Paricalcitol prevented IR-induced tubular injury, evidenced by the prevention of histopathological changes and renal fibrosis with preservation of the activity of ATP-dependent Na+ transporters in the renal cortex. Paricalcitol decreased renal oxidative stress by reducing NADPH oxidase activity and increasing catalase. Paricalcitol also decreased the renal content of TNF-α, IL-6, and AT1R. The NADPH oxidase inhibitor apocynin did not present additive protection to paricalcitol-induced effects. The protective effects of paricalcitol on tubular injury induced by renal IR may dependent on the modulation of redox and proinflammatory signaling and renal angiotensin II/AT1R signaling.
ABSTRACT
Recent evidence indicates that the damaged regions in osteoarthritis are accompanied by the accumulation of iron ions. Ferroptosis, as an iron-dependent form of cell death, holds significant implications in osteoarthritis. Melatonin, a natural product with strong scavenging abilities against reactive oxygen species and lipid peroxidation, plays a crucial role in the treatment of osteoarthritis. This study aims to demonstrate the existence of ferroptosis in osteoarthritis and explore the specific mechanism of melatonin in suppressing ferroptosis and alleviating osteoarthritis. Our findings reveal that melatonin reverses inflammation-induced oxidative stress and lipid peroxidation while promoting the expression of extracellular matrix components in chondrocytes, safeguarding the cells. Our research has revealed that NADPH oxidase 4 (NOX4) serves as a crucial molecule in the ferroptosis process of osteoarthritis. Specifically, NOX4 is located on mitochondria in chondrocytes, which can induce disorders in mitochondrial energy metabolism and dysfunction, thereby intensifying oxidative stress and lipid peroxidation. LC-MS analysis further uncovered that GRP78 is a downstream binding protein of NOX4. NOX4 induces ferroptosis by weakening GRP78's protective effect on GPX4 and reducing its expression. Melatonin can inhibit the upregulation of NOX4 on mitochondria and mitigate mitochondrial dysfunction, effectively suppressing ferroptosis and alleviating osteoarthritis. This suggests that melatonin therapy represents a promising new approach for the treatment of osteoarthritis.
Subject(s)
Ferroptosis , Melatonin , Mitochondria , NADPH Oxidase 4 , Osteoarthritis , Melatonin/pharmacology , Ferroptosis/drug effects , Osteoarthritis/metabolism , Osteoarthritis/drug therapy , Osteoarthritis/pathology , NADPH Oxidase 4/metabolism , Animals , Mitochondria/metabolism , Mitochondria/drug effects , Chondrocytes/metabolism , Chondrocytes/drug effects , Chondrocytes/pathology , Oxidative Stress/drug effects , Lipid Peroxidation/drug effects , Humans , MiceABSTRACT
Introduction: Systemic lupus erythematosus is a multi-faceted autoimmune disorder of complex etiology. Pre-pubertal onset of pediatric systemic lupus erythematosus (pSLE) is uncommon and should raise suspicion for a genetic driver of disease. Autosomal recessive p40 phox deficiency is a rare immunologic disorder characterized by defective but not abolished NADPH oxidase activity with residual production of reactive oxygen species (ROS) by phagocytic cells. Case presentation: We report the case of a now 18-year-old female with pSLE onset at 7 years of age. She presented with recurrent fever and malar rash. Aspects of her immune dysregulation over time have included typical pSLE features including production of autoantibodies, hematologic manifestations, and hypocomplementemia, as well as chronic suppurative skin lesions and recurrent infections. Genetic analysis revealed biallelic pathogenic variants in NCF4 resulting in p40 phox deficiency. Comprehensive NADPH oxidase activity studies confirmed significantly decreased production of reactive oxygen species, confirming the cellular phenotype seen in p40 phox deficient patients. Conclusions: Here, we present a patient with pSLE harboring biallelic variants in NCF4. Our patient represents a unique clinical presentation of severe onset autoimmunity in the setting of a rare inborn error of immunity affecting NADPH oxidase activity. This case underscores the need to consider genetic causes of pSLE in cases of pre-pubertal onset and atypical disease.
ABSTRACT
This review summarises the data from long-term experimental studies and literature data on the role of oxidatively modified low-density lipoproteins (LDL) in atherogenesis and diabetogenesis. It was shown that not "oxidized" (lipoperoxide-containing) LDL, but dicarbonyl-modified LDL are atherogenic (actively captured by cultured macrophages with the help of scavenger receptors), and also cause expression of lectin like oxidized low density lipoprotein receptor 1 (LOX-1) and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 1 (NOX-1) genes in endotheliocytes, which stimulate apoptosis and endothelial dysfunction. The obtained data allowed us to justify new approaches to pharmacotherapy of atherosclerosis and diabetes mellitus.
ABSTRACT
NADPH oxidases (NOXs) are a family of membrane proteins responsible for intracellular reactive oxygen species (ROS) generation by facilitating electron transfer across biological membranes. Despite the established activation of NOXs by protein kinase C (PKC), the precise mechanism through which PKC triggers NOX activation during breast cancer invasion remains unclear. The present study aimed to investigate the role of NOX1 and NOX5 in the invasion of MCF7 human breast cancer cells. The expression and activity of NOXs and matrix metalloprotease (MMP)9 were assessed by reverse transcriptionquantitative PCR and western blotting, and the activity of MMP9 was monitored using zymography. Cellular invasion was assessed using the Matrigel invasion assay, whereas ROS levels were quantified using a FACSCalibur flow cytometer. The findings suggested that NOX1 and NOX5 serve crucial roles in 12Otetradecanoylphorbol13acetate (TPA)induced MMP9 expression and invasion of MCF7 cells. Furthermore, a connection was established between PKC and the NOX1 and 5/ROS signaling pathways in mediating TPAinduced MMP9 expression and cellular invasion. Notably, NOX inhibitors (diphenyleneiodonium chloride and apocynin) significantly attenuated TPAinduced MMP9 expression and invasion in MCF7 cells. NOX1 and NOX5specific small interfering RNAs attenuated TPAinduced MMP9 expression and cellular invasion. In addition, knockdown of NOX1 and NOX5 suppressed TPAinduced ROS levels. Furthermore, a PKC inhibitor (GF109203X) suppressed TPAinduced intracellular ROS levels, MMP9 expression and NOX activity in MCF7 cells. Therefore, NOX1 and NOX5 may serve crucial roles in TPAinduced MMP9 expression and invasion of MCF7 breast cancer cells. Furthermore, the present study indicated that TPAinduced MMP9 expression and cellular invasion were mediated through PKC, thus linking the NOX1 and 5/ROS signaling pathways. These findings offer novel insights into the potential mechanisms underlying their antiinvasive effects in breast cancer.
Subject(s)
Breast Neoplasms , Matrix Metalloproteinase 9 , NADPH Oxidase 1 , NADPH Oxidase 5 , Protein Kinase C , Reactive Oxygen Species , Tetradecanoylphorbol Acetate , Humans , Matrix Metalloproteinase 9/metabolism , Matrix Metalloproteinase 9/genetics , Reactive Oxygen Species/metabolism , NADPH Oxidase 1/metabolism , NADPH Oxidase 1/genetics , NADPH Oxidase 5/metabolism , NADPH Oxidase 5/genetics , Protein Kinase C/metabolism , MCF-7 Cells , Female , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Breast Neoplasms/genetics , Tetradecanoylphorbol Acetate/pharmacology , NADPH Oxidases/metabolism , NADPH Oxidases/genetics , Neoplasm Invasiveness , Cell Movement/drug effects , Gene Expression Regulation, Neoplastic , Signal TransductionABSTRACT
Nicotinamide Adenine Dinucleotide Phosphate (NADPH) plays a vital role in regulating redox homeostasis and reductive biosynthesis. However, if exogenous NADPH can be transported across the plasma membrane has remained elusive. In this study, we present evidence supporting that NADPH can traverse the plasma membranes of cells through a mechanism mediated by the P2X7 receptor (P2X7R). Notably, we observed an augmentation of intracellular NADPH levels in cultured microglia upon exogenous NADPH supplementation in the presence of ATP. The P2X7R-mediated transmembrane transportation of NADPH was validated with P2X7R antagonists, including OX-ATP, BBG, and A-438079, or through P2X7 knockdown, which impeded NADPH transportation into cells. Conversely, overexpression of P2X7 resulted in an enhanced capacity for NADPH transport. Furthermore, transfection of hP2X7 demonstrated the ability to complement NADPH uptake in native HEK293 cells. Our findings provide evidence for the first time that NADPH is transported across the plasma membrane via a P2X7R-mediated pathway. Additionally, we propose an innovative avenue for modulating intracellular NADPH levels. This discovery holds promise for advancing our understanding of the role of NADPH in redox homeostasis and neuroinflammation.
ABSTRACT
Nonalcoholic fatty liver disease (NAFLD) has emerged as a major public health crisis with significant health threats and economic burdens worldwide in the past decades. Betaine, a naturally occurring alkaloid compound present in various dietary sources including spinach and beets, has been shown to ameliorate hepatic lipid metabolism and attenuate NAFLD, while the underlying mechanism remains elusive. Here, we propose a novel mechanism through which betaine exerts its protective effects against hepatic lipid accumulation and NAFLD from an epigenetics perspective. Specifically, we discover that betaine upregulates betaine homocysteine S-methyltransferase (BHMT) expression, leading to increased nicotinamide adenine dinucleotide phosphate (NADPH) production and subsequent upregulation of fat mass and obesity-associated protein (FTO) expression. Increased abundance of FTO targets peroxisome proliferator-activated receptor-gamma coactivator 1-alpha (PGC1α) mRNA and reduces the N6-methyladenosine (m6A) level in the CDS of Ppargc1α transcript, which positively regulates PGC1α expression and subsequently inhibits hepatic lipid accumulation. Overall, our works demonstrate that betaine may be a promising therapeutic strategy for treating NAFLD and improving liver function through the regulation of NADPH and m6A-mediated pathways.
ABSTRACT
Chronic granulomatous disease (CGD) is a group of rare primary inborn errors of immunity characterised by a defect in the phagocyte respiratory burst, which leads to severe and life-threatening infective and inflammatory complications. Despite recent advances in our understanding of the genetic and molecular pathophysiology of X-linked and autosomal recessive CGD, and growth in the availability of functional and genetic testing, there remain significant barriers to early and accurate diagnosis. In the current review, we provide an up-to-date summary of CGD pathophysiology, underpinning current methods of diagnostic testing for CGD and closely related disorders. We present an overview of the benefits of early diagnosis and when to suspect and test for CGD. We discuss current and historical methods for functional testing of NADPH oxidase activity, as well as assays for measuring protein expression of NADPH oxidase subunits. Lastly, we focus on genetic and genomic methods employed to diagnose CGD, including gene-targeted panels, comprehensive genomic testing and ancillary methods. Throughout, we highlight general limitations of testing, and caveats specific to interpretation of results in the context of CGD and related disorders, and provide an outlook for newborn screening and the future.
ABSTRACT
Reduced nicotinamide adenine dinucleotide phosphate (NADPH) is a crucial cofactor in metabolic networks. The efficient regeneration of NADPH is one of the limiting factors for productivity in biotransformation processes. To date, many metabolic engineering tools and static regulation strategies have been developed to regulate NADPH regeneration. However, traditional static regulation methods often lead to the NADPH/NADP+ imbalance, causing disruptions in cell growth and production. These methods also fail to provide real-time monitoring of intracellular NADP(H) or NADPH/NADP+ levels. In recent years, various biosensors have been developed for the detection, monitoring, and dynamic regulate of the intracellular NADP(H) levels or the NADPH/NADP+ balance. These NADPH-related biosensors are mainly used in the cofactor engineering of bacteria, yeast, and mammalian cells. This review analyzes and summarizes the NADPH metabolic regulation strategies from both static and dynamic perspectives, highlighting current challenges and potential solutions, and discusses future directions for the advanced regulation of the NADPH/NADP+ balance.
Subject(s)
Biosensing Techniques , Metabolic Engineering , NADP , NADP/metabolism , Metabolic Engineering/methods , Biosensing Techniques/methods , Humans , Animals , Metabolic Networks and PathwaysABSTRACT
Chronic granulomatous disease (CGD) is a rare inborn error of immunity characterized by recurrent fungal and bacterial infections due to defective nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity. This case report describes an 11-month-old female who was initially diagnosed with tubercular lymphadenitis and presented with fever and bilateral neck swelling. Despite receiving anti-tubercular treatment (ATT) and intravenous antibiotics, the patient experienced recurrent infections and abscesses, prompting further investigation. Laboratory tests revealed normal immunoglobulin levels but abnormal nitroblue tetrazolium (NBT) and dihydrorhodamine (DHR) tests, indicating CGD. Genetic analysis (clinical exome by next-generation sequencing) confirmed a novel NCF2 gene mutation associated with autosomal recessive CGD. This patient was treated with prophylactic antibiotics and antifungals and subsequently underwent successful hematopoietic stem cell transplantation (HSCT). This highlights the diagnostic challenges associated with CGD, particularly in tuberculosis-endemic regions such as India, emphasizing the importance of considering primary immunodeficiency disorders in patients with recurrent infections. Early diagnosis and appropriate treatment, including HSCT, can significantly improve patient outcomes. The patient remained infection-free on prophylactic antimicrobials for 1.5 years post-discharge, demonstrating the potential for a favorable prognosis with timely intervention and comprehensive management.
ABSTRACT
Patients with sickle cell disease (SCD) display an overactive bladder (OAB). Intravascular hemolysis in SCD is associated with various severe SCD complications. However, no experimental studies have evaluated the effect of intravascular hemolysis on bladder function. This study aimed to assess the effects of intravascular hemolysis on the micturition process and the contractile mechanisms of the detrusor smooth muscle (DSM) in a mouse model with phenylhydrazine (PHZ)-induced hemolysis; furthermore, it aimed to investigate the role of intravascular hemolysis in the dysfunction of nitric oxide (NO) signaling and in increasing oxidative stress in the bladder. Mice underwent a void spot assay, and DSM contractions were evaluated in organ baths. The PHZ group exhibited increased urinary frequency and increased void volumes. DSM contractile responses to carbachol, KCl, α-ß-methylene-ATP, and EFS were increased in the PHZ group. Protein expression of phosphorylated endothelial NO synthase (eNOS) (Ser-1177), phosphorylated neuronal NO synthase (nNOS) (Ser-1417), and phosphorylated vasodilator-stimulated phosphoprotein (VASP) (Ser-239) decreased in the bladder of the PHZ group. Protein expression of oxidative stress markers, NOX-2, 3-NT, and 4-HNE, increased in the bladder of the PHZ group. Our study shows that intravascular hemolysis promotes voiding dysfunction correlated with alterations in the NO signaling pathway in the bladder, as evidenced by reduced levels of p-eNOS (Ser-1177), nNOS (Ser-1417), and p-VASP (Ser-239). The study also showed that intravascular hemolysis increases oxidative stress in the bladder. Our study indicates that intravascular hemolysis promotes an OAB phenotype similar to those observed in patients and mice with SCD.
ABSTRACT
Reactive oxygen species (ROS) is a collective term for highly reactive oxygen derivatives, including singlet oxygen, hydroxyl radicals, superoxide anions, and hydrogen peroxide. In plants, ROS are produced in apoplasts, chloroplasts, mitochondria, and peroxisomes. Although ROS are toxic when their levels exceed a certain threshold, low-concentration ROS can serve as essential signaling molecules for plant growth and development, as well as plant responses to abiotic and biotic stresses. Various aspects of the role of ROS in plants have been discussed in previous reviews. In this review, we first summarize recent progress in the regulatory mechanisms of apoplastic ROS signaling and then propose its potential roles in plant defense against vascular pathogens to provide new ideas for the prevention and control of vascular diseases.
ABSTRACT
NADPH, the primary source of reducing equivalents in the cytosol, is used in vertebrate rod photoreceptor outer segments to reduce the all-trans retinal released from photoactivated visual pigment to all-trans retinol. Light activation of the visual pigment isomerizes the 11-cis retinal chromophore to all-trans, thereby destroying it and necessitating its regeneration. Release and reduction of all-trans retinal are the first steps in the series of reactions that regenerate the visual pigment. Glucose and glutamine can both support the reduction of all-trans retinal to retinol, indicating that the NADPH used in rod photoreceptor outer segments can be generated by the pentose phosphate pathway as well as by mitochondria-linked pathways. We have used the conversion of all-trans retinal to all-trans retinol to examine whether amino acids other than glutamine can also support the generation of NADPH in rod photoreceptors. We have measured this conversion in single isolated mouse rod photoreceptors by imaging the fluorescence of the all-trans retinal and retinol generated after exposure of the cells to light. In agreement with previous work, we find that 5 mM glucose or 0.5 mM glutamine support the conversion of â¼70-80% of all-trans retinal to retinol, corresponding to a reduced NADP fraction of â¼10%. All other amino acids at 0.5 mM concentration support the conversion to a much lesser extent, indicating reduced NADP fractions of 1-2% at most. Taurine was also ineffective at supporting NADPH generation, while formic acid, the toxic metabolite of methanol, suppressed the generation of NADPH by either glucose or glutamine.
Subject(s)
Glutamine , Mice, Inbred C57BL , NADP , Retinal Rod Photoreceptor Cells , Vitamin A , Animals , NADP/metabolism , Mice , Glutamine/metabolism , Retinal Rod Photoreceptor Cells/metabolism , Vitamin A/metabolism , Retinaldehyde/metabolism , Glucose/metabolismABSTRACT
Biotransformation is a process in which molecules are modified in the presence of a biocatalyst or enzymes, as well as the metabolic alterations that occur in organisms from exposure to the molecules. Microbial biotransformation is an important process in natural product drug discovery as novel compounds are biosynthesised. Additionally, biotransformation products offer compounds with improved efficacy, solubility, reduced cytotoxic and allows for the understanding of structure activity relationships. One of the driving forces for these impeccable findings are associated with the presence of cytochrome P450 monooxygenases that is present in all organisms such as mammals, bacteria, and fungi. Numerous fungal strains have been used and reported for their ability to biotransform different compounds. This review focused on studies using Alternaria species as biocatalysts in the biotransformation of natural product compounds. Alternaria species facilitates reactions that favour stereoselectivity, regioselectivity under mild conditions. Additionally, microbial biotransformation products, their application in food, pharmaceutical and agricultural sector is discussed in this review.
ABSTRACT
Cuproptosis is characterized by lipoylated protein aggregation and loss of iron-sulfur (Fe-S) proteins, which are crucial for a wide range of important cellular functions, including DNA replication and damage repair. Sirt2 and sirt4 are lipoamidases that remove the lipoyl moiety from lipoylated proteins using nicotinamide adenine dinucleotide (NAD+) as a cofactor. However, to date, it is not clear whether nicotinamide mononucleotide (NMN), a precursor of NAD+, affects cellular sensitivity to cuproptosis. Therefore, in the current study, cuproptosis was induced by the copper (Cu) ionophore elesclomol (Es) in HeLa cells. It was also found that Es/Cu treatment increased cellular DNA damage level. On the other hand, NMN treatment partially rescued cuproptosis in a dose-dependent manner, as well as reduced cellular DNA damage level. In addition, NMN upregulated the expression of Fe-S protein POLD1, without affecting the aggregation of lipoylated proteins. Mechanistic study revealed that NMN increased the expression of sirt2 and cellular reduced nicotinamide adenine dinucleotide phosphate (NADPH) level. Overexpression of sirt2 and sirt4 did not change the aggregation of lipoylated proteins, however, sirt2, but not sirt4, increased cellular NADPH levels and partially rescued cuproptosis. Inhibition of NAD+ kinase (NADK), which is responsible for generating NADPH, abolished the rescuing function of NMN and sirt2 for Es/Cu induced cell death. Taken together, our results suggested that DNA damage is a characteristic feature of cuproptosis. NMN can partially rescue cuproptosis by upregulating sirt2, increase intracellular NADPH content and maintain the level of Fe-S proteins, independent of the lipoamidase activity of sirt2.
Subject(s)
DNA Damage , NADP , Nicotinamide Mononucleotide , Sirtuin 2 , Up-Regulation , Humans , Sirtuin 2/metabolism , Sirtuin 2/genetics , HeLa Cells , NADP/metabolism , DNA Damage/drug effects , Up-Regulation/drug effects , Nicotinamide Mononucleotide/pharmacology , Nicotinamide Mononucleotide/metabolism , Copper/pharmacology , Copper/metabolism , Sirtuins/metabolismABSTRACT
Nicotinamide Adenine Dinucleotide Phosphate (NAD(P)H) plays an important role in numerous biologically significant redox reactions. The photochemical restoration of its oxidized form (NAD(P)+) under physiological conditions is intriguing in the context of integrated photo and catalysis. Herein, we report the functionalized graphitic carbon-based solar light active photocatalyst by doping boron and fluorine in the native graphitic carbon nitride (GCN) (nonfunctionalized) for the regeneration of enzymatically visible light active coenzyme and in photo-acetalization reactions. The metal-free functionalized photocatalyst systems such as BFGCN-x leads to higher yield NADH and NADPH regeneration. They are also capable of catalyzing acetal reactions in the absence of any Lewis and Bronsted acids. The current research endeavor provides the advancement and the application of functionalized GCN-based photocatalysts for NADH (61.89%), NADPH (59.84%) regeneration, and photo-acetalization reactions.
ABSTRACT
The recent birth of the immunometabolism field has comprehensively demonstrated how the rewiring of intracellular metabolism is critical for supporting the effector functions of many immune cell types, such as myeloid cells. Among all, the transcriptional regulation mediated by Hypoxia-Inducible Factors (HIFs) and Nuclear factor erythroid 2-related factor 2 (NRF2) have been consistently shown to play critical roles in regulating the glycolytic metabolism, redox homeostasis and inflammatory responses of macrophages (Mφs). Although both of these transcription factors were first discovered back in the 1990s, new advances in understanding their function and regulations have been continuously made in the context of immunometabolism. Therefore, this review attempts to summarize the traditionally and newly identified functions of these transcription factors, including their roles in orchestrating the key events that take place during glycolytic reprogramming in activated myeloid cells, as well as their roles in mediating Mφ inflammatory responses in various bacterial infection models.