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Potential therapeutic role of spermine via Rac1 in osteoporosis:Insights from zebrafish and mice

Zoological Research 2024年第2期45卷 367-380页

作者： Rui-Xue Jiang Nan Hu Yu-Wei Deng Long-Wei Hu Hao Gu Nan Luo Jin Wen Xin-Quan Jiang Department of Prosthodontics Shanghai Ninth People’s HospitalShanghai Jiao Tong University School of MedicineShanghai 200011China College of Stomatology Shanghai Jiao Tong UniversityNational Center for StomatologyNational Clinical Research Center for Oral DiseasesShanghai Key Laboratory of StomatologyShanghai Research Institute of StomatologyShanghai Engineering Research Center of Advanced Dental Technology and MaterialsShanghai 200125China Department of Endodontics Shanghai Ninth People’s HospitalShanghai Jiao Tong University School of MedicineShanghai Jiao Tong UniversityShanghai 200011China Department of Oral and Maxillofacial-Head and Neck Oncology Shanghai Ninth People’s HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200011China Department of Preventive Dentistry Shanghai Ninth People’s HospitalShanghai Jiao Tong University School of MedicineShanghai Jiao Tong UniversityShanghai 200011China

Osteoporosis(OP)is a prevalent metabolic bone disease.While drug therapy is essential to prevent bone loss in osteoporotic patients,current treatments are limited by side effects and high costs,necessitating the development of more effective and safer targeted therapies.Utilizing a zebrafish(Danio rerio)larval model of osteoporosis,we explored the influence of the metabolite spermine on bone homeostasis.Results showed that spermine exhibited dual activity in osteoporotic zebrafish larvae by increasing bone formation and decreasing bone resorption.spermine not only demonstrated excellent biosafety but also mitigated prednisolone-induced embryonic neurotoxicity and cardiotoxicity.Notably,spermine showcased protective attributes in the nervous systems of both zebrafish embryos and larvae.At the molecular level,Rac1 was identified as playing a pivotal role in mediating the antiosteoporotic effects of spermine,with P53 potentially acting downstream of Rac1.These findings were confirmed using mouse(Mus musculus)models,in which spermine not only ameliorated osteoporosis but also promoted bone formation and mineralization under healthy conditions,suggesting strong potential as a bonestrengthening agent.This study underscores the beneficial role of spermine in osteoporotic bone homeostasis and skeletal system development,highlighting pivotal molecular mediators.Given their efficacy and safety,human endogenous metabolites like spermine are promising candidates for new anti-osteoporotic drug development and daily bone-fortifying agents.

关键词： Osteoporosis spermine Rac1 Zebrafish Mice

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Supramolecular cyclization induced emission enhancement in a pillar[5]arene probe for discrimination of spermine

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Chinese Chemical Letters 2024年第1期35卷 275-279页

作者： Yibin Zhou Hao Tang Hanlun Wu Xiaomei Jiang Lingyun Wang Derong Cao State Key Laboratory of Luminescent Materials and Devices School of Chemistry and Chemical EngineeringSouth China University of TechnologyGuangzhou 510641China

Early diagnosis and treatment of cancer requires the development of tools that are both sensitive and selective in detecting spermine.In this study,we presented a"supramolecular cyclization-induced emission enhancement"strategy for the sensitive and selective detection of spermine.A new pillar[5]arene probe(P1)demonstrated excellent solution/solid dual-state emission properties,and the addition of certain spermine(Spm)resulted in fluorescence enhancement due to the synergy of multiple weak interactions that restricted the free motion of P1 in the P1⊃Spm complex.This mechanism was further confirmed by time-resolved spectroscopy,DFT calculations,and IGM analysis.With its low limit of detection and high selectivity,P1 is a promising tool for measuring spermine in artificial urine samples.

关键词： spermine Pillararene Probe Supramolecular chemistry Supramolecular cyclization induced emission enhancement

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spermine protects intestinal barrier integrity through ras-related C3 botulinum toxin substrate 1/phospholipase C-γ1 signaling pathway in piglets

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Animal Nutrition 2022年第1期8卷 135-143页

作者： Guangmang Liu Xiaomei Xu Caimei Wu Gang Jia Hua Zhao Xiaoling Chen Gang Tian Jingyi Cai Jing Wang Institute of Animal Nutrition Sichuan Agricultural UniversityChengdu611130China Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education Chengdu611130China Maize Research Institute Sichuan Agricultural UniversityChengdu611130China

Weaning stress can cause tight junctions damage and intestinal permeability enhancement,which leads to intestinal imbalance and growth retardation,thereby causing damage to piglet growth and development.spermine can reduce stress.However,the mechanism of spermine modulating the intestinal integrity in pigs remains largely unknown.This study aims to examine whether spermine protects the intestinal barrier integrity of piglets through ras-related C3 botulinum toxin substrate 1(Rac1)/phospholipase C-g1(PLC-γ1)signaling pathway.In vivo,80 piglets were categorised into 4 control groups and 4 spermine groups(10 piglets per group).The piglets were fed with normal saline or spermine at 0.4 mmol/kg BW for 7 h and 3,6 and 9 d.In vitro,we investigated whether spermine protects the intestinal barrier after a tumor necrosis factor a(TNF-a)challenge through Rac1/PLC-γ1 signaling pathway.The in vivo study found that spermine supplementation increased tight junction protein mRNA levels and Rac1/PLC-γ1 signaling pathway gene expression in the jejunum of piglets.The serum D-lactate content was significantly decreased after spermine supplementation(Pspermine increased the levels of tight junction protein expression,Rac1/PLC-γ1 signaling pathway and transepithelial electrical resistance,and decreased paracellular permeability(Pspermine supplementation enhanced the levels of tight junction protein expression,Rac1/PLC-γ1 signaling pathway and transepithelial electrical resistance,and decreased paracellular permeability compared with the NSC-23766 and U73122 treatment with spermine after TNF-a challenge(Pspermine protects intestinal barrier integrity through Rac1/PLC-γ1 signaling pathway in piglets.

关键词： spermine Intestinal barrier Rac1/PLC-γ1 signaling pathway Intestinal integrity

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New insights into the role of spermine in enhancing the antioxidant capacity of rat spleen and liver under oxidative stress

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Animal Nutrition 2017年第1期3卷 85-90页

作者： Xianjian Wu Wei Cao Gang Jia Hua Zhao Xiaoling Chen Caimei Wu Jiayong Tang Jing Wang Guangmang Liu Institute of Animal Nutrition Sichuan Agricultural University Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education Maize Research Institute Sichuan Agricultural University

Oxidative stress can damage cellular antioxidant defense and reduce livestock production efficiency.spermine is a ubiquitous cellular component that plays important roles in stabilizing nucleic acids,modulating cell growth and differentiation, and regulating ion channel activities. spermine has the potential to alleviate the effects of oxidative stress. However, to date no information is available about the effect of spermine administration on antioxidant property of the liver and spleen in any mammalian in vivo system. This study aims to investigate the protective effect of spermine on rat liver and spleen under oxidative stress. Rats received intragastric administration of either 0.4 μmol/g body weight of spermine or saline once a day for 3 days. The rats in each treatment were then injected with either diquat or sterile saline at 12 mg/kg body weight. Liver and spleen samples were collected 48 h after the last spermine ingestion.Results showed that regardless of diquat treatment, spermine administration significantly reduced the malondialdehyde(MDA) content by 23.78% in the liver and by 5.75% in the spleen, respectively(P spermine administration also enhanced the catalase(CAT) activity, anti-hydroxyl radical(AHR) capacity and glutathione(GSH) content by 38.68%, 15.53% and 1.32% in the spleen, respectively(Pspermine administration and diquat injection about anti-superoxide anion(ASA),AHR capacity, CAT activity, GSH content, and total antioxidant capacity(T-AOC) in the liver and about ASA capacity and T-AOC in the spleen of weaned rats(P spermine administration significantly increased the AHR capacity, CAT activity, GSH content, and T-AOC by 40.23%,31.15%, 30.25%, 35.37% in the liver, respectively(P spermine + diquat group significantly increased ASA capacity by 15.63% in the liver and by 73.41% in the spleen of we

关键词： spermine Oxidative stress Antioxidant capacity Spleen Liver

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spermine increases bactericidal activity of silver-nanoparticles against clinical methicillin-resistant Staphylococcus aureus

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Chinese Chemical Letters 2018年第12期29卷 1824-1828页

作者： Chang Liu Han Shen Su Wang Xiaoli Cao Hongpan Xu Yanyan Xia Tingting Bai Yufeng Liu Lijun Peng Chuchu Li Zhirui Guo Zhiyang Li Department of Clinical Laboratory The Affiliated Drum Tower Hospital of Nanjing University Medical SchoolNanjing 210008China Department of Geriatrics The Second Affiliated HospitalKey Laboratory for Aging&DiseaseNanjing Medical UniversityNanjing 210011China College of Life Science Yangtze UniversityJingzhou 434025China Department of Technical Services Jiangsu Provincial Center for Disease Prevention and ControlNanjing 210009China

Methicillin-resistant Staphylococcus aureus(MRSA) has emerged worldwide as a major multidrugresistant pathogen that causes notable morbidity and mortality. Fast emerging of MRSA prevalence requires special attention for strengthening the inventory of antimicrobial compounds. Silver nanoparticles(AgNPs) have been widely used to treat multi-drug resistant pathogens due to the unique antibacterial properties, meanwhile spermine has been proven to exert outstanding inhibition effect to S.aureus with not yet fully understood mechanisms. The aim of this study was to investigate the synergistic effect of AgNPs and spermine as well as to determine the antibacterial activity of their combination against MRSA strains. Several clinical MRSA isolates and ATCC BAA-1026 were used to determine minimum inhibitory concentration(MIC) and fractional inhibitory concentration indices(FICI) of AgNPs and spermine, and a synergistic effect was observed. This phenomenon was further confirmed by growth curve and time-killing assays, showed that spermine could be used as an adjuvant for AgNPs in the treatment of MRSA infections.

关键词： spermine Silver nanoparticles Staphylococcus aureus Synagistic effect Antimicrobial

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spermine——AN INHIBITION OF in vitro CAPACITATION AND FERTILIZATION IN HAMSTER SPERM

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Chinese Science Bulletin 1989年第21期34卷 1820-1825页

作者：石其贤钟翠玲叶蓁刘良初 Zhejiang Academy of Medicine Hangzhou 310013 PRC

I. INTRODUCTION The polyamines, putrescine, spermidine and spermine exist in all mammalian tissues and fluids. In semen, spermine is frequently present in high concentrations. However, the

关键词： spermine sperm inhibitor capacitalion fertilization

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Effects of spermine supplementation on the morphology, digestive enzyme activities, and antioxidant capacity of intestine in weaning rats

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Animal Nutrition 2016年第4期2卷 370-375页

作者： Tingting Fang Gang Jia Hua Zhao Xiaoling Chen Jiayong Tang Jing Wang Guangmang Liu Institute of Animal Nutrition Sichuan Agricultural University Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education Maize Research Institute Sichuan Agricultural University

The main objective of this study was to investigate the effects of different doses of spermine and its extended supplementation on the morphology, digestive enzyme activities, and intestinal antioxidant capacity in weaning rats. Nineteen-day-old male rats received intragastric spermine at doses of 0.2 and0.4 μmol/g BW for 3 or 7 d, whereas control rats received similar doses of saline. The results are as follows: 1) In the jejunum, the seven-day supplementation with both doses of spermine significantly increased crypt depth(P spermine dose increased villus height and crypt depth(P spermine dose significantly increased villus height and crypt depth compared with the control group for 7 days(P spermine dose increased alkaline phosphatase activity in the jejunum(P spermine dose relative to those in the control groups after 3 and 7 d; moreover, the anti-superoxide anion(ASA) and glutathione(GSH) contents increased with the high spermine dose that lasted for 3 days(P spermine dose compared with those of the low spermine dose(P spermine dose decreased the MDA content and ASA and T-AOC activities(P spermine supplementation can modulate gut development and enhance the antioxidant status of the jejunum in weaning rats, and a dosage of 0.4 μmol spermine/g BW had better effects than the dosage of 0.2 μmol spermine/g BW on accelerating gut development and incr

关键词： Antioxidant capacity Enzymes activities Morphology spermine Weaning rats

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Metagenomes of polyamine-transforming bacterioplankton along a nearshore-open ocean transect

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Marine Life Science & Technology 2022年第2期4卷 268-276页

作者： Xinxin Lu Kai Wang Xiaozhen Mou Department of Biological Sciences Kent State UniversityKentOHUSA

Short-chained aliphatic polyamines (PAs) have recently been recognized as an important carbon, nitrogen, and/or energy source for marine bacterioplankton. To study the genes and taxa involved in the transformations of different PA compounds and their potential variations among marine systems, we collected surface bacterioplankton from nearshore, offshore, and open ocean stations in the Gulf of Mexico and examined their metagenomic responses to additions of single PA model compounds (putrescine, spermidine, or spermine). Genes affiliated with PA uptake and all three known PA degradation pathways, i.e., transamination, γ-glutamylation, and spermidine cleavage, were significantly enriched in most PA-treated metagenomes. In addition, identified PA-transforming taxa were mostly the alpha and gamma classes of Proteobacteria, with less important contributions from members of Betaproteobacteria, Actinobacteria, Bacteroidetes, Cyanobacteria, Firmicutes, and Planctomycetes. These findings suggest that PA transformations are ubiquitous, have diverse pathways, and are carried out by a broad range of the bacterioplankton taxa in the Gulf of Mexico. Identified PA-transforming bacterial genes and taxa were different among nearshore, offshore, and open ocean sites, but were little different among individual compound-amended metagenomes at any specific site. These observations further indicate that PA-transforming taxa and genes are site-specific and with high similarities among PA compounds.

关键词： Polyamines Microbial transformation Putrescine Spermidine spermine

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Casein kinase G may be the target of spermine during progesterone-induced oocyte maturation

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Cell Research 1993年第1期3卷 61-74页

作者： LI RUNSHENG AND JIAKE TSOShanghai Institute of Cell Biology, Academia Sinica Shanghai Institute of Cell Biology Academia Sinica

Casein kinase G (CKG) with more than 2500-fold enrichment was purified from Bufo bufo gargarizans ovaries.The catalytic activity of the enzyme was found to be associated with its 42 kD subunit, and its 26 kD subunit was found to be the major target for the enzyme auto phosphorylation. Each full-grown oocyte contained 1.9 units of CKG corresponding to an intracellular concentration of 93 nM. After injecting an amount of 0.38 units of the enzyme into the oocyte, approximately 50％ of the progesterone-induced maturation was inhibited. The inhibitory effect was enhanced in oocytes pretreated with spermine, which was consistent with the results that the enzyme was activated in vitro in the presence of spermine. The MPF-induced oocyte maturation was delayed and even prohibited in the kinase-microinjected oocytes.A 55 kD oocyte protein was identified as an substrate of CKG both in vivo and in vitro, and the enhancement of the 55 kD protein phosphorylation was associated with kinase inhibition on maturation and on protein synthesis in kinase-microinjected oocytes. As the endogenous spermine level decreased in the course of progesterone induced oocyte maturation, 55 kD protein was dephospho rylated. Heparin, a specific inhibitor of CKG, potentiated the progesterone-induced oocyte maturation. Altogether the experimental results indicated strongly that CKG may be the physiological target of spermine.

关键词： casein kinase G spermine toad oocyte progesterone induced maturation.

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Studies on the physiological function of spermine in the process of progesterone induced toad oocyte maturation

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Cell Research 1992年第2期2卷 103-117页

作者： JlAKE TSO Shanghai Institute of Cell Biology Academia Sinica

Spermidine or spermine but not putrescine inhibitedprogesterone induced Bufo bufo gargarizans oocyte matura-tion.The IDfor spermine inhibition via intra-oocyte mi-croinjection on maturation induced by progesterone was 6.8mM(100 nl).spermine could inhibit MPF induced toadoocyte maturation with a much higher ID. A 55 kD protein was dephosphorylated during the pro-cess of progesterone induced oocyte maturation.spermineselectively promoted the level of phosphorylation of thisprotein in both progesterone-stimulated and hormone-un-treated oocytes.The extent of its dephosphorylation wasfairly correlated with the percentage of GVBD in the hor-mone stimulated oocytes. The level of endogenous spermine was reduced by 28%between the period of 0.40 GVBDand 0.60 GVBD,atwhich 55 kD protein was dephosphorylated. spermine inhibited progesterone-stimulated proteinsynthesis in almost the same dose dependent manner as itsinhibitory effect on the hormone-induced maturation.Theendogenous spermine regulated 55 kD protein dephosphory-lation which may trigger the increase of protein synthesisand in turn promote the activation of MPF.It is possiblethat 55 kD protein may be one of the components of messen-ger ribonucleoprotein(mRNP)particles.

关键词： spermine toad oocyte progesterone induced maturation.

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