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Transcriptome analysis shows nicotinamide seed treatment alters expression of genes involved in defense and epigenetic processes in roots of seedlings of Picea abies

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Journal of Forestry Research 2022年第4期33卷 1365-1375页

作者： Cecilia Laurell Torkel Berglund Anna B.Ohlsson Department of Industrial Biotechnology School of Engineering Sciences in ChemistryBiotechnology and Health(CBH)KTH Royal Institute of Technology10691 StockholmSweden

nicotinamide treatment of plants and plant cell cultures has been shown to promote defense and decrease levels of DNA methylation.In the present study,we used RNA-seq technology to study overall changes in gene expression induced in roots of 3-month-old spruce(Picea abies)seedlings grown from nicotinamide-treated seeds to examine the molecular mechanisms underlying the defense promotion.Approximately 350 genes were identified as differentially expressed in roots after the seed treatment.Stress response genes,including transcription factors MYB77 and LHY and two chitinase enzymes,were generally upregulated,whereas genes thought to be involved in epigenetic regulation such as DDM1,known to promote DNA methylation,were present at high frequency among the downregulated genes.Across all samples,the expression of downregulated epigenetic-related genes was highly correlated with the nicotinamide treatment,indicating a common regulation.Our results support an earlier hypothesis regarding a potential role of nicotinamide as a defense-signal mediator.

关键词： DNA methylation Large-scale gene expression analysis nicotinamide Picea abies Seed treatment

nicotinamide suppresses bevacizumab-induced epithelial-mesenchymal transition of ARPE-19 cells by attenuating oxidative stress

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International Journal of Ophthalmology(English edition) 2021年第4期14卷 481-488页

作者： Li Zhou De-Peng Shi Wen-Juan Chu Shan Song Xiang-Hui Hao Ling-Ling Yang Hai-Feng Xu Medical College Qingdao UniversityQingdao 266071Shandong ProvinceChina State Key Laboratory Cultivation Base Shandong Provincial Key Laboratory of OphthalmologyShandong Eye InstituteShandong First Medical University&Shandong Academy of Medical SciencesQingdao 266071Shandong ProvinceChina Qingdao Eye Hospital Shandong Eye InstituteShandong First Medical University&Shandong Academy of Medical SciencesQingdao 266071Shandong ProvinceChina

AIM:To investigate the effects of nicotinamide(NAM)on bevacizumab(BEV)-induced epithelial-mesenchymal transition(EMT)of human retinal pigment epithelial cells(ARPE-19)and the underling mechanisms.METHODS:ARPE-19 cells were treated with BEV for 24,48,and 72 h,and the variation degrees of EMTrelated markers(fibronectin,α-SMA,vimentin,and ZO-1)were assessed by Western blotting to select the optimal treatment time point which exhibited the most obvious changes of EMT-related markers for the subsequent experiments.Furthermore,NAM was added to the medium,the m RNA and protein levels of the EMT-related markers were then measured.The accumulation of reactive oxygen species(ROS)and H_(2)O_(2) and the total antioxidant capacity(TAC)of the cells were also measured to evaluate the level of oxidative stress.RESULTS:After being treated with BEV for 72 h,the protein expression levels of EMT-related markers in ARPE-19 cells showed significant changes.Meanwhile the levels of ROS and H_(2)O_(2) were obviously increased,and the TAC of ARPE-19 cells was decreased.Totally 72 h was chosen to be the optimal treatment time point in subsequentexperiments.Furthermore,NAM inhibited BEV-induced EMT by downregulating fibronectin,α-SMA,and vimentin and upregulating ZO-1,decreased the accumulation of ROS and H_(2)O_(2),and enhanced TAC in BEV-treated ARPE-19 cells.CONCLUSION:This study demonstrates that NAM suppressed BEV-induced EMT in ARPE-19 cells by attenuating oxidative stress.Hence,NAM may be a potential therapeutic agent for alleviating neovascular fibrosis of the ocular fundus after anti-vascular endothelial growth factor therapy.

关键词： nicotinamide epithelial-mesenchymal transition bevacizumab oxidative stress ARPE-19 cells

Supplementation of nicotinamide mononucleotide improves the quality of postovulatory aged porcine oocytes

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Journal of Molecular Cell Biology 2022年第4期14卷 69-71页

作者： Yilong Miao Zhaokang Cui Xiaotong Zhu Qian Gao Bo xiong College of Animal Science and Technology Nanjing Agricultural UniversityNanjing210095China College of Veterinary Medicine Nanjing Agricuitural UniversityNanjing 210095China

Dear Editor,Postovulatory aging would occur to impair the oocyte quality in a timedependent manner if ovulated oocytes are not fertilized within the optimal timing in the oviduct or in the dishes(Trapphoff et al.,2016),which might result in the early pregnancy failure in vivo and adverse outcome of assisted reproductive technology(ART)in vitro(Nagy et al.,1993;Wilcox et al.,1998).However,the effective approaches to preventing the postovulatory aging-induced oocyte deterioration are still underexplored.We recently reported that supplementation of nicotinamide mononucleotide(NMN),a synthetic precursor of NAD+,which is an essential cofactorfor enzymes'functioning in almost all critical cellularmetabolic reactions(Imai and Guarente,2014;Canto et al.,2015),reverses the declining quality of maternally aged mouse oocytes(Miao et al.,2020).

关键词： nicotinamide critical optimal

Effects of different concentrations of nicotinamide on hematopoietic stem cells cultured in vitro

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World Journal of Stem Cells 2024年第2期16卷 163-175页

作者： Yan Ren Yan-Ni Cui Hong-Wei Wang The Second Clinical Medical College Shanxi Medical UniversityTaiyuan 030001Shanxi ProvinceChina Department of Hematology The Second Hospital of Shanxi Medical UniversityTaiyuan 030001Shanxi ProvinceChina Department of Hematology Key Laboratory of Molecular Diagnosis and Treatment of Blood Diseases in Shanxi ProvinceTaiyuan 030001Shanxi ProvinceChina

BACKGROUND In vitro expansion to increase numbers of hematopoietic stem cells(HSCs)in cord blood could improve clinical efficacy of this vital resource.nicotinamide(NAM)can promote HSC expansion ex vivo,but its effect on hematopoietic stem and progenitor cells(HSPCs,CD34^(+)CD38)and functional subtypes of HSCs-shortterm repopulating HSCs(ST-HSCs,CD34^(+)CD38CD45RACD49f^(+))and long-term repopulating HSCs(LT-HSCs,CD34^(+)CD38CD45RACD49f^(+)CD90^(+))is not yet known.As a sirtuin 1(SIRT1)inhibitor,NAM participates in regulating cell adhesion,polarity,migration,proliferation,and differentiation.However,SIRT1 exhibits dual effects by promoting or inhibiting differentiation in different tissues or cells.We propose that the concentration of NAM may influence proliferation,differentiation,and SIRT1 signaling of HSCs.AIM To evaluate the effects and underlying mechanisms of action of different concentrations of NAM on HSC proliferation and differentiation.METHODS CD34^(+)cells were purified from umbilical cord blood using MacsCD34 beads,and cultured for 10-12 d in a serum-free medium supplemented with cytokines,with different concentrations of NAM added according to experimental requirements.Flow cytometry was used to detect phenotype,cell cycle distribution,and apoptosis of the cultured cells.Real-time polymerase chain reaction was used to detect the transcription levels of target genes encoding stemness-related factors,che mokines,components of hypoxia pathways,and antioxidant enzymes.Dichloro-dihydro-fluorescein diacetate probes were used to evaluate intracellular production of reactive oxygen species(ROS).Determination of the effect of different culture conditions on the balance of cytokine by cytometric bead array.RESULTS Compared with the control group,the proportion and expansion folds of HSPCs(CD34^(+)CD38)incubated with 5 mmol/L or 10 mmol/L NAM were significantly increased(all P<0.05).The ST-HSCs ratio and fold expansion of the 5 mmol/L NAM group were significantly higher than those of the control and 10 mmol/L N

关键词： Hematopoietic stem cells nicotinamide Concentration Proliferation Differentiation Sirtuin 1

nicotinamide-Induced Apoptosis Can Be Enhanced by Melatonin in Mouse Myeloma Cells

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Tsinghua Science and Technology 2006年第4期11卷 408-414页

作者：张贵友盛鸿智刘佳 Department of Biological Sciences and Biotechnology Tsinghua University Beijing 100084 China College of Life Sciences Shandong Agricultural University Taian 271018 China

The mechanism of apoptosis induced by nicotinamide was investigated by treating mouse myeloma cells （Sp2/0） with various concentrations of nicotinamide. The typical hallmarks of apoptosis, including chromatin condensation and DNA fragmentation, were detected when cells were treated with nicotinamide at concentrations of 30, 40, 50, and 60 mmol/L. The apoptosis percentage increased with increasing nicotinamide concentration. Interestingly, the strong antioxidant melatonin did not restrain the apoptosis induced by nicotinamide in mouse myeloma cells but greatly increased the induction of nicotinamide on apoptosis. When cells were preincubated with 0.1, 1, and 10 mmol/L melatonin before nicotinamide induction, the percentage of apoptosis induced by 50 mmol/L nicotinamide markedly increased with increasing melatonin concentration. These results suggest that apoptosis induced by nicotinamide has no relationship with oxida tive stress and melatonin could enhance nicotinamide-induced apoptosis in mouse myeloma cells by stimulating cell division in a certain manner. nicotinamide may provide a new method to treat some kinds of tumors with no damage to normal tissues.

关键词： apoptosis nicotinamide melatonin mouse myeloma cells

nicotinamide reverses liver fibrosis in a thioacetamide induced mouse model

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Nicotinamide reverses liver fibrosis in a thioacetamide indu...

Effects of nicotinamide and riboflavin on the biodesulfurization activity of dibenzothiophene by Rhodococcus erythropolis USTB-03

2018年中国质谱学术大会（CMSC2018）

作者： Zhaoyun Zong Jing Liu Jie Jin Haiteng Deng MOE Key Laboratory of Bioinformatics School of Life SciencesTsinghua University

Liver fibrosis is a common liver disease mainly due to chronic viral hepatitis, high fat diet and alcoholism. Previous studies have shown that reactive oxygen species(ROS) are produced during this process. nicotinamide adenine dinucleotide(NAD+) as a vital hydrogen carrier for redox enzymes plays important roles in redox reactions of cells. As a major NAD+ precursor, nicotinamide(NAM) can synthesize NAD+ by salvage pathway. This study investigates the therapy roles of NAM in liver fibrosis by using a thioactamide induced mouse model. The results show that NAM reverses liver fibrosis in a mouse model induced by thioacetamide. Furthermore, metabolomics and proteomics analysis reveals that NAM suppresses the activation of hepatic stellate cells via maintaining vitamin A content and inhibiting the expression of SMAD2 in hepatic stellate cells. In conclusion, these findings provide new insights into a potential treatment against liver fibrosis.

关键词： NAD+ nicotinamide liver fibrosis

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Journal of Environmental Sciences 2008年第5期20卷 613-618页

作者： YAN Hai SUN Xudong XU Qianqian MA Zhao XIAO Chengbin Ning Jun Department of Biological Science and Technology School of Applied Science University of Science and Technology Beijing Beijing 100083 China Research Center for Eco-environmental Science Chinese Academy of Sciences Beijing 100085 China

Rhodococcus erythropolis USTB-03 is a promising bacterial strain for the biodesulfurization of dibenzothiophene （DBT） via a sulfurspecific pathway in which DBT is converted to 2-hydroxybiphenyl （2HBP） as an end product. The effects of nicotinamide and riboflavin on the sulfur specific activity （SA） of DBT biodesulfurization by R. erythropolis USTB-03 were investigated. Both nicotinamide and riboflavin were found to enhance the expression of SA, which was not previously reported. When R. erythropolis USTB-03 was grown on a medium containing nicotinamide of 10.0 mmol or riboflavin of 50.0 μmol, SA was raised from 68.0 or so to more than 130 mmol 2HBP/（kg dry cells.h）. When R. erythropolis USTB-03 was grown in the presence of both nicotinamide of 5.0 mmol and riboflavin of 25.0 μmol, SA was further increased to 159.0 mmol 2HBP/（kg dry cells.h）. It is suggested that the biological synthesis of reduced form of flavin mononucleotide （FMNH2）, an essential coenzyme for the activities of biodesulfurization enzyme Dsz C and A, might be enhanced by nicotinamide and riboflavin, which was responsible for the increased SA of R. erythropolis USTB-03.

关键词： biodesulfurization dibenzothiophene nicotinamide Rhodococcus erythropolis USTB-03 riboflavin

Effect of nicotinamide on newly diagnosed type 1 diabetic children

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Acta Pharmacologica Sinica 2006年第6期27卷 724-727页

作者： Madeeha KAMAL Abdul-JabbarAlABBASY AhoodAlMUSLEMANI Abdulbari BENER Department of Pediatrics Salmaniya Medical ComplexManamaBahrain School of Health Department of PediatricsHamad Medical CorporationDohaQatar Department of Pediatrics.Salmaniya Medical Complex ManamaBahrain Department of Medical Statistics and Epidemiology Hamad General HospitalHamad Medical CorporationDohaQatar Department of Evidence for Population Health Unit School of Epidemiology and Health SciencesUniversity of ManchesterManchester.UK

Aim:To determine whether a low dose of nicotinamide(NA)therapy for pediatricpatients with type 1 diabetes,initiated within the first 24 h of diagnosis,prolongsthe"honeymoon"period and lowers their insulin requirements.Methods:Allchildren(n=66)with newly diagnosed type 1 diabetes admitted to Salmaniya MedicalComplex between 1998 and 2000,received NA 1-2 mg/kg per day,in addition tosc insulin bid.The patients were followed for 24 months(NA group).Findings inthis group were compared with records from a similarly diagnosed control group(n=37),who were admitted to the same hospital between 1995 and 1997 and did notreceive NA treatment.The insulin dose per kg bodyweight required at baselineand at 3-monthly intervals up to 2 years after diagnosis was determined.Results:At baseline,the two groups did not differ with respect to age,ethnic background,weight,insulin dose per kg bodyweight or glucose levels on admission.However,NA group had lower insulin requirements than control group at each 3-monthinterval up to 2 years after diagnosis.Conclusion:Our study results suggest thateven low doses of oral NA given to children with newly diagnosed type 1 diabetesmay reduce insulin requirements and prolong the"honeymoon"period.

关键词： type 1 diabetes nicotinamide insulin therapy insulin dose glycated hemoglobin A

Apoptosis Induced by High Concentrations of nicotinamide in Tobacco Suspension Cells

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Tsinghua Science and Technology 2004年第1期9卷 88-93页

作者：张贵友朱瑞宇戴尧仁 Department of Biological Sciences and Biotechnology Tsinghua University Beijing 100084 China

As an inhibitor of poly(ADP-ribose) polymerase (PARP), nicotinamide has a restraining effect on apoptosis at certain low concentrations. In our present study, apoptosis induced by high concentrations of nicotinamide was observed in tobacco suspension cells. When cells were preincubated with 250 mmol/L nicotinamide for 24 h, the hallmarks of apoptosis were detected, including DNA fragments increasing in size by multiples of 180-200 bp, the condensation and peripheral distribution of nuclear chromatin, and a positive reaction to the TUNEL assay. At the same time, the degradation of PARP and the reduction in the potential of the inner membrane of mitochondria appeared in apoptotic cells induced by high concentrations of nicotinamide. This result indicates that apoptosis induced by high concentrations of nicotinamide is associated with caspase-3-like activity and with the opening of mitochondrial permeability pores. These results partially support the hypothesis that high concentrations of PARP inhibitor could force cells to enter an apoptotic pathway by delay of DNA repair in replicating cells.

关键词： apoptosis nicotinamide tobacco suspension cell poly (ADP-ribose) polymerase