目的探讨乙醇脱氢核酶ribox02与NAD^+、NADH特异性结合的位点以及结合力性质。方法通过选择性2-OH酰基化学探测法(selective 2-hydroxyl acylation analyzed by primer extension,SHAPE)探测ribox02的二级结构;利用等温滴定量热法(isoth...目的探讨乙醇脱氢核酶ribox02与NAD^+、NADH特异性结合的位点以及结合力性质。方法通过选择性2-OH酰基化学探测法(selective 2-hydroxyl acylation analyzed by primer extension,SHAPE)探测ribox02的二级结构;利用等温滴定量热法(isothermal titratio calorimetry,ITC)进一步测定ribox02与NADH、NAD^+的亲和力强度及作用力性质;通过紫外交联法精确定位NAD^+、NADH与ribox02 RNA的特异性结合位点。结果直接解析ribox02的二级结构,并发现核酶ribox02与NADH、NAD^+的相互作用力为范德华力或氢键作用,且ribox02与NADH的相互作用力较之与NAD^+更为强烈,ribox02与NADH、NAD^+的特异性结合位点为23G、24U、25U、38U、72U、73U、74U、75G和95G。结论通过ribox02的二级结构及其与NAD^+、NADH的相互作用揭示了核酶ribox02与NAD^+/NADH特异性结合位点以及结合力性质。展开更多
Aging is a complex issue due to its nature in progressive physiological and functional decay. As better medicine, technology, and living conditions became accessible to many people, the longevity of human beings incre...Aging is a complex issue due to its nature in progressive physiological and functional decay. As better medicine, technology, and living conditions became accessible to many people, the longevity of human beings increased during the past centuries. Recent research established vital roles for NAD＋ and its precursors in protecting and maintaining the redox homeostasis in cells, which might be applicable therapeutically to prevent cell degeneration. Notably, the contribution of NAD＋ metabolites to lifespan extension in model systems indicates that the potential beneficial effects of NAD＋ precursors. In this mini review, by introducing the background of NAD＋-consuming enzymes in ＂caloric restriction＂, we focus on NAD＋ and its precursors in diet, with further emphasis on its association with health and diseases. We also provide insights in future utilization ofNAD＋ and its precursors as nutrition supplement for lifespan extension.展开更多
2025年6月19日,上海交通大学医学院王戈林团队在Molecular Cell杂志上发表了题为“The NAMPT enzyme employs a switch that directly senses AMP/ATP and regulates cellular responses to energy stress”的研究论文。该研究首次揭示N...2025年6月19日,上海交通大学医学院王戈林团队在Molecular Cell杂志上发表了题为“The NAMPT enzyme employs a switch that directly senses AMP/ATP and regulates cellular responses to energy stress”的研究论文。该研究首次揭示NAD^(+)合成关键酶烟酰胺磷酸核糖转移酶(NAMPT)可直接感应AMP/ATP变化,兼具“能量传感器”与“NAD^(+)合成控制开关”的双重功能,协调ATP和NAD^(+)2条基本能量代谢通路,为缺血性脑卒中等疾病的治疗提供了潜在药物靶点。展开更多
BACKGROUND Glycolysis provides growth advantages and leads to drug resistance in colorectal cancer(CRC)cells.SIRT1,an NAD+-dependent deacetylase,regulates various cellular processes,and its upregulation results in ant...BACKGROUND Glycolysis provides growth advantages and leads to drug resistance in colorectal cancer(CRC)cells.SIRT1,an NAD+-dependent deacetylase,regulates various cellular processes,and its upregulation results in antitumor effects.This study investigated the role of SIRT1 in metabolic reprogramming and oxaliplatin resistance in CRC cells.AIM To investigate the role of SIRT1 in metabolic reprogramming and overcoming oxaliplatin resistance in CRC cells.METHODS We performed transcriptome sequencing of human CRC parental cells and oxaliplatin-resistant cells to identify differentially expressed genes.Key regulators were identified via the LINCS database.NAD+levels were measured by flow cytometry,and the effects of SIRT1 on oxaliplatin sensitivity were assessed by MTS assays,colony formation assays,and xenograft models.Glycolytic function was measured using Western blot and Seahorse assays.RESULTS Salermide,a SIRT1 inhibitor,was identified as a candidate compound that enhances oxaliplatin resistance.In oxaliplatin-resistant cells,SIRT1 was downregulated,whereasγH2AX and PARP were upregulated.PARP activation led to NAD+depletion and SIRT1 inhibition,which were reversed by PARP inhibitor treatment.The increase in SIRT1 expression overcame oxaliplatin resistance,and while SIRT1 inhibition increased glycolysis,the increase in SIRT1 inhibited glycolysis in resistant CRC cells,which was charac-terized by reduced expression of the glycolytic enzymes PKM2 and LDHA,as well as a decreased extracellular acidification rate.The PKM2 inhibitor shikonin inhibited glycolysis and reversed oxaliplatin resistance induced by SIRT1 inhibition.CONCLUSION SIRT1 expression is reduced in oxaliplatin-resistant CRC cells due to PARP activation,which in turn increases glycolysis.Restoring SIRT1 expression reverses oxaliplatin resistance in CRC cells,offering a promising therapeutic strategy to overcome drug resistance.展开更多
Mitochondria are semi-autonomous organelles present in eukaryotic cells,containing their own genome and transcriptional machinery.However,their functions are intricately linked to proteins encoded by the nuclear genom...Mitochondria are semi-autonomous organelles present in eukaryotic cells,containing their own genome and transcriptional machinery.However,their functions are intricately linked to proteins encoded by the nuclear genome.Mitochondrial transcription termination factors(mTERFs)are nucleic acid-binding proteins involved in RNA splicing and transcription termination within plant mitochondria and chloroplasts.Despite their recognized importance,the specific roles of mTERF proteins in maize remain largely unexplored.Here,we clone and functionally characterize the maize mTERF18 gene.Our findings reveal that mTERF18 mutations lead to severely undifferentiated embryos,resulting in abortive phenotypes.Early kernel exhibits abnormal basal endosperm transfer layer and a significant reduction in both starch and protein accumulation in mterf18.We identify the mTERF18 gene through mapping-based cloning and validate this gene through allelic tests.mTERF18 is widely expressed across various maize tissues and encodes a highly conserved mitochondrial protein.Transcriptome data reveal that mTERF18 mutations disrupt transcriptional termination of the nad6 gene,leading to undetectable levels of Nad6 protein and reduced complex I assembly and activity.Furthermore,transmission electron microscopy observation of mterf18 endosperm uncover severe mitochondrial defects.Collectively,these findings highlight the critical role of mTERF18 in mitochondrial gene transcription termination and its pivotal impact on maize kernel development.展开更多
2025年6月3日,北京大学药学院天然药物及仿生药物全国重点实验室谢海燕教授团队与南开大学庞代文教授合作,在Nature Biomedical Engineering杂志发表了题为“NAD+biosynthesis and mitochondrial repair in acute kidney injury via ult...2025年6月3日,北京大学药学院天然药物及仿生药物全国重点实验室谢海燕教授团队与南开大学庞代文教授合作,在Nature Biomedical Engineering杂志发表了题为“NAD+biosynthesis and mitochondrial repair in acute kidney injury via ultrasound-responsive thylakoid-integrating liposomes”的研究论文,该研究开发了一种可超声驱动的新型仿生脂质类囊体系统,通过重塑肾细胞内的NAD+能量代谢过程,高效恢复胞内能量供给和抗氧化能力,治疗急性肾损伤(AKI)。展开更多
目的在兰科石斛属药用植物鉴定中应用新的分子标记。方法扩增并测定9种石斛属植物线粒体中NADH脱氢酶亚基1编码基因(nad 1)内含子2(in tron 2)的全长序列。结果比对后的nad 1 in tron 2序列长872bp,其中有17个变异位点,可以鉴别除粉花石...目的在兰科石斛属药用植物鉴定中应用新的分子标记。方法扩增并测定9种石斛属植物线粒体中NADH脱氢酶亚基1编码基因(nad 1)内含子2(in tron 2)的全长序列。结果比对后的nad 1 in tron 2序列长872bp,其中有17个变异位点,可以鉴别除粉花石斛D end robium lodd ig esii以外的8种植物。结论线粒体nad 1 in tron2序列可以作为一种新的分子标记用于石斛属植物的鉴定。展开更多
文摘目的探讨乙醇脱氢核酶ribox02与NAD^+、NADH特异性结合的位点以及结合力性质。方法通过选择性2-OH酰基化学探测法(selective 2-hydroxyl acylation analyzed by primer extension,SHAPE)探测ribox02的二级结构;利用等温滴定量热法(isothermal titratio calorimetry,ITC)进一步测定ribox02与NADH、NAD^+的亲和力强度及作用力性质;通过紫外交联法精确定位NAD^+、NADH与ribox02 RNA的特异性结合位点。结果直接解析ribox02的二级结构,并发现核酶ribox02与NADH、NAD^+的相互作用力为范德华力或氢键作用,且ribox02与NADH的相互作用力较之与NAD^+更为强烈,ribox02与NADH、NAD^+的特异性结合位点为23G、24U、25U、38U、72U、73U、74U、75G和95G。结论通过ribox02的二级结构及其与NAD^+、NADH的相互作用揭示了核酶ribox02与NAD^+/NADH特异性结合位点以及结合力性质。
基金We gratefully acknowledge the National Natural Science Foundation of China （No. 21502026）, Shenzhen Science and Technology Innovation Committee （JCYJ20140411112047887） for their support to Yanchao Pan. We thank Dr. Zhen Xie for comments on the manuscript.
文摘Aging is a complex issue due to its nature in progressive physiological and functional decay. As better medicine, technology, and living conditions became accessible to many people, the longevity of human beings increased during the past centuries. Recent research established vital roles for NAD＋ and its precursors in protecting and maintaining the redox homeostasis in cells, which might be applicable therapeutically to prevent cell degeneration. Notably, the contribution of NAD＋ metabolites to lifespan extension in model systems indicates that the potential beneficial effects of NAD＋ precursors. In this mini review, by introducing the background of NAD＋-consuming enzymes in ＂caloric restriction＂, we focus on NAD＋ and its precursors in diet, with further emphasis on its association with health and diseases. We also provide insights in future utilization ofNAD＋ and its precursors as nutrition supplement for lifespan extension.
文摘2025年6月19日,上海交通大学医学院王戈林团队在Molecular Cell杂志上发表了题为“The NAMPT enzyme employs a switch that directly senses AMP/ATP and regulates cellular responses to energy stress”的研究论文。该研究首次揭示NAD^(+)合成关键酶烟酰胺磷酸核糖转移酶(NAMPT)可直接感应AMP/ATP变化,兼具“能量传感器”与“NAD^(+)合成控制开关”的双重功能,协调ATP和NAD^(+)2条基本能量代谢通路,为缺血性脑卒中等疾病的治疗提供了潜在药物靶点。
基金Supported by the National Natural Science Foundation of China,No.82072756Beijing Xisike Clinical Oncology Research Foundation,No.Y-HR2019-0285.
文摘BACKGROUND Glycolysis provides growth advantages and leads to drug resistance in colorectal cancer(CRC)cells.SIRT1,an NAD+-dependent deacetylase,regulates various cellular processes,and its upregulation results in antitumor effects.This study investigated the role of SIRT1 in metabolic reprogramming and oxaliplatin resistance in CRC cells.AIM To investigate the role of SIRT1 in metabolic reprogramming and overcoming oxaliplatin resistance in CRC cells.METHODS We performed transcriptome sequencing of human CRC parental cells and oxaliplatin-resistant cells to identify differentially expressed genes.Key regulators were identified via the LINCS database.NAD+levels were measured by flow cytometry,and the effects of SIRT1 on oxaliplatin sensitivity were assessed by MTS assays,colony formation assays,and xenograft models.Glycolytic function was measured using Western blot and Seahorse assays.RESULTS Salermide,a SIRT1 inhibitor,was identified as a candidate compound that enhances oxaliplatin resistance.In oxaliplatin-resistant cells,SIRT1 was downregulated,whereasγH2AX and PARP were upregulated.PARP activation led to NAD+depletion and SIRT1 inhibition,which were reversed by PARP inhibitor treatment.The increase in SIRT1 expression overcame oxaliplatin resistance,and while SIRT1 inhibition increased glycolysis,the increase in SIRT1 inhibited glycolysis in resistant CRC cells,which was charac-terized by reduced expression of the glycolytic enzymes PKM2 and LDHA,as well as a decreased extracellular acidification rate.The PKM2 inhibitor shikonin inhibited glycolysis and reversed oxaliplatin resistance induced by SIRT1 inhibition.CONCLUSION SIRT1 expression is reduced in oxaliplatin-resistant CRC cells due to PARP activation,which in turn increases glycolysis.Restoring SIRT1 expression reverses oxaliplatin resistance in CRC cells,offering a promising therapeutic strategy to overcome drug resistance.
基金supported by the National Key Research and Development Program of China(2021YFF1000304)the National Natural Science Foundation of China(32222060)Anhui Agricultural University(RC422404)to J.Y.
文摘Mitochondria are semi-autonomous organelles present in eukaryotic cells,containing their own genome and transcriptional machinery.However,their functions are intricately linked to proteins encoded by the nuclear genome.Mitochondrial transcription termination factors(mTERFs)are nucleic acid-binding proteins involved in RNA splicing and transcription termination within plant mitochondria and chloroplasts.Despite their recognized importance,the specific roles of mTERF proteins in maize remain largely unexplored.Here,we clone and functionally characterize the maize mTERF18 gene.Our findings reveal that mTERF18 mutations lead to severely undifferentiated embryos,resulting in abortive phenotypes.Early kernel exhibits abnormal basal endosperm transfer layer and a significant reduction in both starch and protein accumulation in mterf18.We identify the mTERF18 gene through mapping-based cloning and validate this gene through allelic tests.mTERF18 is widely expressed across various maize tissues and encodes a highly conserved mitochondrial protein.Transcriptome data reveal that mTERF18 mutations disrupt transcriptional termination of the nad6 gene,leading to undetectable levels of Nad6 protein and reduced complex I assembly and activity.Furthermore,transmission electron microscopy observation of mterf18 endosperm uncover severe mitochondrial defects.Collectively,these findings highlight the critical role of mTERF18 in mitochondrial gene transcription termination and its pivotal impact on maize kernel development.
文摘2025年6月3日,北京大学药学院天然药物及仿生药物全国重点实验室谢海燕教授团队与南开大学庞代文教授合作,在Nature Biomedical Engineering杂志发表了题为“NAD+biosynthesis and mitochondrial repair in acute kidney injury via ultrasound-responsive thylakoid-integrating liposomes”的研究论文,该研究开发了一种可超声驱动的新型仿生脂质类囊体系统,通过重塑肾细胞内的NAD+能量代谢过程,高效恢复胞内能量供给和抗氧化能力,治疗急性肾损伤(AKI)。
文摘目的在兰科石斛属药用植物鉴定中应用新的分子标记。方法扩增并测定9种石斛属植物线粒体中NADH脱氢酶亚基1编码基因(nad 1)内含子2(in tron 2)的全长序列。结果比对后的nad 1 in tron 2序列长872bp,其中有17个变异位点,可以鉴别除粉花石斛D end robium lodd ig esii以外的8种植物。结论线粒体nad 1 in tron2序列可以作为一种新的分子标记用于石斛属植物的鉴定。
