SENSORS AND ACTUATORS B-CHEMICAL
·
2018
·
IF 5.667
Shuyun Zhu,Cuihua Lei,Jing Sun,Xian-En Zhao,Xiao Wang,Xiaolu Yan,Wei Liu,Hua Wang
In the present study, a novel colorimetric sensing platform was constructed for probing the NAD + /NADH-dependent biocatalytic transformations. Manganese dioxide (MnO 2 ) nanosheets as an oxidase-mimicking nanomaterial could directly oxidize 3,3′,5,5′-tetramethylbenzidine (TMB) into oxTMB without the need of H 2 O 2 . Importantly, it was found that NADH could easily trigger the decomposition of MnO 2 nanosheets, causing the decrease of solution absorbance. This is demonstrated by the enzyme catalysis reactions of two dehydrogenase models, ethanol dehydrogenase (ADH) and lactate dehydrogenase (LDH), where NADH is formed and consumed, respectively, in their physiological enzymatic reactions. A MnO 2 -TMB sensing platform was thereby proposed for the analysis of their catalytic reaction substrates including ethanol and pyruvic acid. The detection limits of ethanol and pyruvic acid can reach 5.0 μM and 100 nM, respectively. The developed optical biosensing platform can be used to develop other dehydrogenase-based biosensors followed by monitoring their substrates.
研究领域:
生物化学
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纳米生物学
·
分析化学
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产品关联
DOI
高影响因子
MOLECULAR CELL
·
2024
·
IF 14.5
Chuanlong Wang,Qingyi Chen,Siyuan Chen,Lijuan Fan,Zhending Gan,Muyang Zhao,Lexuan Shi,Peng Bin,Guan Yang,Xihong Zhou,Wenkai Ren
Serine metabolism is involved in the fate decisions of immune cells; however, whether and how de novo serine synthesis shapes innate immune cell function remain unknown. Here, we first demonstrated that inflammatory macrophages have high expression of phosphoglycerate dehydrogenase (PHGDH, the rate-limiting enzyme of de novo serine synthesis) via nuclear factor κB signaling. Notably, the pharmacological inhibition or genetic modulation of PHGDH limits macrophage interleukin (IL)-1β production through NAD+ accumulation and subsequent NAD+-dependent SIRT1 and SIRT3 expression and activity. Mechanistically, PHGDH not only sustains IL-1β expression through H3K9/27 acetylation-mediated transcriptional activation of Toll-like receptor 4 but also supports IL-1β maturation via NLRP3-K21/22/24/ASC-K21/22/24 acetylation-mediated activation of the NLRP3 inflammasome. Moreover, mice with myeloid-specific depletion of Phgdh show alleviated inflammatory responses in lipopolysaccharide-induced systemic inflammation. This study reveals a network by which a metabolic enzyme, involved in de novo serine synthesis, mediates post-translational modifications and epigenetic regulation to orchestrate IL-1β production, providing a potential inflammatory disease target.
研究领域:
免疫学
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代谢
·
炎症
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产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2021
·
IF 12.479
Yang Tian,Wen-Li Jiang,Wen-Xin Wang,Guo-Jiang Mao,Yongfei Li,Chun-Yan Li
The reduced coenzymes (NADH and NADPH) are an important product in energy metabolism and closely related to the occurrence and development of cancer. So it is necessary to use a powerful detection tool to visualize NAD(P)H in energy metabolism of tumor cells and find a new strategy to improve cancer treatment based on NAD(P)H. Herein, a novel multifunctional probe (Cy-N) is synthesized with good near-infrared fluorescence (NIRF) response to NAD(P)H and the photoacoustic (PA) and photothermal properties are successfully activated by NAD(P)H. The probe is successfully applied in visualizing NAD(P)H in energy metabolism of tumor cells and imaging NAD(P)H in bacteria. Moreover, the probe can be used to image NAD(P)H in energy metabolism of tumor-bearing mice by dual-modal imaging (NIRF and PA). More importantly, in terms of the role of NAD(P)H in energy metabolism, the photothermal therapy (PTT) is activated by NAD(P)H and a novel strategy of enhanced PTT is proposed by injecting glucose. As far as we know, this is the first probe to detect NAD(P)H in energy metabolism through dual-modal imaging, and also the first probe to activate PTT based on NAD(P)H, which will provide important information of the diagnosis and treatment of cancer.
研究领域:
生物化学
·
医学影像学
·
癌症治疗
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产品关联
DOI
PubMed
高影响因子
ANALYTICAL BIOCHEMISTRY
·
2016
·
IF 2.243
Wei Zhang,Min Zhu,Feng Wang,Danhui Cao,Jennifer Jin Ruan,Weike Su,Benfang Helen Ruan
Glutamate dehydrogenase (GDH) catalyzes the oxidative deamination of L-glutamate and is important for several biological processes . For GDH inhibitor screening, we developed a novel mono-sulfonated tetrazolium salt (EZMTT), which can be synthesized using H 2 O 2 oxidation and purified easily on silica gel in large quantities. The EZMTT detection method showed linear dose responses to NAD(P)H, dehydrogenase concentration and cell numbers. In E. coli GDH assay, the EZMTT method showed excellent assay reproducibility with a Z factor of 0.9 and caused no false positives in the presence of antioxidants (such as BME). Using the EZMTT-formazan-NAD(P)H system, we showed that EGCG is a potent E. coli GDH inhibitor (IC 50 45 nM) and identified that Ebselen , a multifunctional thioredoxin reductase inhibitor, inactivated E. coli GDH (IC 50 213 nM). In cell-based assays at 0.5 mM tetrazolium concentration, EZMTT showed essentially no toxicity after a 3-day incubation, whereas 40% of inhibition was observed for WST-8. In conclusion, EZMTT is a novel tetrazolium salt which provides improved features that are suitable for dehydrogenases and real-time cell-based high-throughput screening (HTS).
研究领域:
生物化学
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药物筛选
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2023
·
IF 9.5
Ying Zhang,Bin Wei,Hao Liang
An organometallic complex-catalyzed artificial coenzyme regeneration system has attracted widespread attention. However, the combined use of organometallic complex catalysts and natural enzymes easily results in mutual inactivation. Herein, we establish a rhodium-based metal–organic framework (MOF)-on-MOF difunctional core–shell nanoreactor as an artificial enzymatic NAD(P)H regeneration system. UiO67 as the core is used to capture rhodium molecules for catalyzing NAD(P)H regeneration. UiO66 as the shell is used to specifically immobilize His-tagged lactate dehydrogenase (LDH) and serve as a protection shield for LDH and [Cp*Rh(bpy)Cl]+ to prevent mutual inactivation. A variety of results indicate that UiO67@Rh@UiO66 has good activity in realizing NAD(P)H regeneration. Noteworthily, UiO67@Rh@UiO66@LDH maintains a high activity level even after 10 cycles. This work reports a novel NAD(P)H regeneration platform to open up a new avenue for constructing chemoenzyme coupling systems.
研究领域:
生物化学
·
材料科学
·
酶工程
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产品关联
DOI
PubMed
高影响因子
Cells
·
2024
·Vol. 13
·期 21
·1799
·
IF 5.1
Seongsu Kang,Jiwon Park,Zhihong Cheng,Sanghyun Ye,Seung-Hyun Jun,Nae-Gyu Kang
Nicotinamide adenine dinucleotide (NAD + ) is indispensable for the regulation of biological metabolism. Previous studies have revealed its role in aging and degenerative diseases, while crucially showing that supplementation with NAD + or its precursors could ameliorate or reverse the progression of aging. Despite extensive evidence for the role and action of NAD + in aging, its pharmacological activity on the skin, or even its mechanism, has not been elucidated. In this study, we established a novel approach to effectively utilize NAD + for skin anti-aging by enhancing the pharmacological efficacy of exogenous NAD + using a phytochemical complex consisting of quercetin, and enoxolone through inhibition of CD38. Through the comprehensive in vitro experiments based on human fibroblasts, we observed that exogenous NAD + could exert protective effects against both extrinsic aging induced by ultraviolet light exposure and intrinsic aging. Additionally, we found that its effects were significantly boosted by quercetin and enoxolone. In this in-depth study, we demonstrated that these beneficial effects are mediated by improved sirtuin activation, autophagy, and mitochondrial functionality. Our approach is expected to verify the applicability of the topical application of NAD + and offer more effective solutions for the unmet needs of patients and consumers who demand more effective anti-aging effects.
研究领域:
生物化学
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药理学
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皮肤科学
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产品关联
DOI
PubMed
高影响因子
NEW JOURNAL OF CHEMISTRY
·
2022
·Vol. 46
·期 13
·6274-6282
·
IF 3.925
Xiu Xing,Yan Liu,Ming-Liang Shi,Kun Li,Xin-Yue Fan,Zhong-Liu Wu,Na Wang,Xiao-Qi Yu
Controllable and mild photoenzymatic production of chiral alcohols was realized by coupling a versatile photochemical NAD(P)H regeneration system with (R)- or (S)-selective ketoreductases. The efficiency of NAD(P)H regeneration was improved using a Rhodium functionalized metal organic framework, namely Rh-UiO-67, to adjust and control electron transport and electron utilization. Furthermore, six different ketoreductases could be successfully immobilized on Rh-UiO-67 and combined with the light-driven NAD(P)H regeneration system to produce chiral aryl alcohols. Various chiral alcohols with complementary (R)- and (S)-conformations can be constructed by this method with high yields (97%) and excellent stereoselectivity (>99% ee).
研究领域:
化学
·
生物化学
·
催化
·
有机合成
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产品关联
DOI
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2025
·
IF 4.7
Hongtao Duan,Rui Zhang,Aiminuer Asikaer,Liang Pan,Shui Wang,Kuilong Huang,Deshuai Lou,Yuanqiang Wang,Zhihua Lin,Yan Shen
Background & Aims: Acute pancreatitis (AP) is a life-threatening condition, and hypertriglyceridemia (HTG) is recognized as a factor exacerbating AP and impeding pancreatic regeneration. Nicotinamide mononucleotide (NMN), a precursor in the biosynthesis of nicotinamide adenine dinucleotide (NAD + ), is extensively utilized to restore NAD + levels. However, the impact of NMN on HTG-AP has not been previously addressed, which prompted our investigation into its effects and underlying mechanisms in this study. Methods & Results: Here, through bioinformatics analysis and in vivo experiments, we identified abnormalities in the thioredoxin system. In vitro studies revealed that NMN rescued oleic acid (OA)- and palmitic acid (PA)-induced mitochondrial dysfunction and cellular injury in pancreatic acinar cells by suppressing thioredoxin-interacting protein (TXNIP) through NAD + /sirtuin 1 (SIRT1) signaling. Repeated administration of NMN significantly ameliorated P407 and caerulein (CER)-induced pancreatic injury and dysfunction in mice. Consistently, NMN exhibited the potential to reduce inflammatory responses, lower serum lipid levels, and mitigate the accumulation of reactive oxygen species (ROS). More importantly, sustained NMN treatment inhibited the NOTCH pathway and promoted M2-type macrophage dominance during the pancreatic repair phase, influencing early or late macrophage polarization, which significantly enhanced inflammation resolution. As expected, in vitro models using mouse bone marrow-derived macrophage (BMDM), RAW 264.7, and THP-1 cells confirmed that NMN influences macrophage phenotype through the NOTCH pathway. Conclusions: Therefore, NMN ameliorates pancreatic acinar cell injury via NAD + /SIRT1-mediated TXNIP suppression and may influence macrophage polarization by inhibiting NOTCH activation, offering a novel therapeutic strategy for the treatment and repair of HTG-AP.
研究领域:
医学
·
生物化学
·
分子生物学
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产品关联
DOI
PubMed
高影响因子
Chemical Science
·
2019
·Vol. 10
·期 35
·8179-8186
·
IF 9.556
Xiaohong Pan,Yuehui Zhao,Tingting Cheng,Aishan Zheng,Anbin Ge,Lixin Zang,Kehua Xu,Bo Tang
Reductive stress, the opposite of oxidative stress, represents a disorder in the redox balance state which is harmful to biological systems. For decades, the role of oxidative stress in tumor therapy has been the focus of attention, while the effects of reductive stress have been rarely studied. Here, we report the anti-cancer effects of reductive stress induced by three natural antioxidants (resveratrol, curcumin and celastrol). Considering the fact that the solid tumor microenvironment suffers from hypoxia, we performed cell experiments under hypoxic conditions. In order to observe the reductive stress, we first developed an ultrasensitive fluorescent probe (TCF-MQ) for specifically imaging NAD(P)H which is a marker of reductive stress. TCF-MQ responded to NAD(P)H rapidly and exhibited high sensitivity with a detection limit of 6 nM. With the help of TCF-MQ, we found that upon the treatment of HepG2 cells with pharmacological doses of three natural antioxidants under hypoxic conditions, high levels of NAD(P)H were produced before cell death. The excess NAD(P)H resulted in reductive stress instead of oxidative stress. In contrast, under normoxic conditions, there was no reductive stress involved in the process of cell death induced by three natural antioxidants. Therefore, we hypothesize that the mechanism of cancer cell death induced by natural antioxidants under hypoxia should be attributed to the reductive stress.
研究领域:
生物化学
·
肿瘤学
·
药理学
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产品关联
DOI
PubMed
高影响因子
Cell Metabolism
·
2019
·
IF 22.415
Sofie Lautrup,David A. Sinclair,Mark P. Mattson,Evandro F. Fang
NAD + is a pivotal metabolite involved in cellular bioenergetics, genomic stability, mitochondrial homeostasis, adaptive stress responses, and cell survival. Multiple NAD + -dependent enzymes are involved in synaptic plasticity and neuronal stress resistance. Here, we review emerging findings that reveal key roles for NAD + and related metabolites in the adaptation of neurons to a wide range of physiological stressors and in counteracting processes in neurodegenerative diseases, such as those occurring in Alzheimer’s, Parkinson’s, and Huntington diseases, and amyotrophic lateral sclerosis. Advances in understanding the molecular and cellular mechanisms of NAD + -based neuronal resilience will lead to novel approaches for facilitating healthy brain aging and for the treatment of a range of neurological disorders.
研究领域:
神经科学
·
分子生物学
·
神经病学
·
衰老研究
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DOI
PubMed
高影响因子
PLoS One
·
2013
·Vol. 8
·期 9
·e74100
·
IF 3.73
Heyu Chen,Yao Wang,Jixi Zhang,Yingxin Ma,Caixia Wang,Ying Zhou,Hongchen Gu,Weihai Ying
Aim
To test the hypothesis that NAD + -carrying mesoporous silica nanoparticles (M-MSNs@NAD+) can effectively deliver NAD + into cells to produce cytoprotective effects.
Methods & Materials
NAD + was incorporated into M-MSNs. Primary rat astrocyte cultures and PC12 cells were treated with H 2 O 2 , followed by post-treatment with M-MSNs@NAD+. After various durations of the post-treatment, intracellular NAD + levels, intracellular ATP levels and lactate dehydrogenase (LDH) release were determined.
Results & Discussion
M-MSNs can be effectively loaded with NAD + . The M-MSNs@NAD+ can significantly attenuate H 2 O 2 -induced NAD + and ATP decreases in both astrocyte cultures and PC12 cells. M-MSNs@NAD+ can also partially prevent the H 2 O 2 -induced LDH release from both astrocyte cultures and PC12 cells. In contrast, the NAD + that is spontaneously released from the M-MSNs@NAD+ is insufficient to prevent the H 2 O 2 -induced damage.
Conclusions
Our study has suggested the first approach that can effectively deliver NAD + into cells, which provides an important basis both for elucidating the roles of intracellular NAD + in biological functions and for therapeutic applications of NAD + . Our study has also provided the first direct evidence demonstrating a key role of NAD + depletion in oxidative stress-induced ATP decreases.
研究领域:
神经科学
·
分子生物学
·
纳米技术
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产品关联
DOI
PubMed
高影响因子
ELECTROCHIMICA ACTA
·
2020
·
IF 6.215
Fei Zhang,Xingxing Wu,Jiaojiao Gao,Yimai Chen,Yawen Gui,Ling Zhang,Wei Gan,Qunhui Yuan
Herein, we developed an efficient anode catalyst for alcohol biofuel cell by integrating multi-walled carbon nanotubes (MWCNTs) into an isoreticular metal organic framework derived porous carbon. The derived porous carbon (PC) intercalated by MWCNTs (PC/MWCNTs) serviced as the anode component in catalyzing the electrooxidation of reduced β-Nicotinamide adenine dinucleotide (NADH), enabling catalysis to ethanol electrooxidation by alcohol dehydrogenase with NAD + as both free coenzyme and electron transfer mediators (onset potential, 0.14 V vs. SCE, pH 8.0). Hierarchy of PC/MWCNTs with micro-, meso-, and macropores provides improved immobilization of electroactive enzymes, aids the facile transportations of electrolyte and increases the conductivity and specific surface areas of anode and results in a much higher catalytic current density for NADH (1.17 mA cm −2 for 10 mM NADH, pH 9.0) and alcohol bioanode (maximum steady-state current density, 0.25 ± 0.03 mA cm −2 , pH 8.0) than its singular component analogues (PC and MWCNTs). The high Michaelis-Menten constant (166 ± 16.8 mM) favorites the detection of ethanol at high concentrations. The linear range of ethanol is 10–300 mM, with the sensitivity and detection limit as 24 nA mM −1 and 3 mM. The study applies porous carbon nanomaterials as both electrocatalysts for coenzyme and scaffolds for enzymes, benefiting to feasible constructions of bioelectrodes with notable current densities.
研究领域:
材料科学
·
电化学
·
生物催化
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产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）