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Amino acids regulate energy utilization through mammalian target of rapamycin complex 1 and adenosine monophosphate activated protein kinase pathway in porcine enterocytes

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Animal Nutrition 2020年第1期6卷 98-106页

作者： Hao Xiao Cuifang Zha Fangyuan Shao Li Wang Bi’e Tan State Key Laboratory of Livestock and Poultry Breeding Ministry of Agriculture Key Laboratory of Animal Nutrition and Feed Science in South ChinaGuangdong Public Laboratory of Animal Breeding and NutritionGuangdong Key Laboratory of Animal Breeding and NutritionInstitute of Animal ScienceGuangdong Academy of Agricultural SciencesGuangzhou510640China Hunan Provincial Key Laboratory of Animal Nutritional Physiology and Metabolic Process Key Laboratory of Agro-ecological Processes in Subtropical RegionNational Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry ProductionInstitute of Subtropical AgricultureChinese Academy of SciencesChangsha410125China Faculty of Health Sciences University of MacaoMacaoChina College of Animal Science and Technology Hunan Agricultural UniversityChangsha410128China

As major fuels for the small intestinal mucosa,dietary amino acids(AA)are catabolized in the mitochondria and serve as sources of energy *** present study was conducted to investigate AA metabolism that supply cell energy and the underlying signaling pathways in porcine *** porcine epithelial cells(IPEC-J2)were treated with different concentrations of AA,inhibitor,or agonist of mammalian target of rapamycin complex 1(mTORCl)and adenosine monophosphate activated protein kinase(AMPK),and mitochondrial respiration was *** results showed that AA treatments resulted in enhanced mitochondrial respiration,increased intracellular content of pyruvic acid and lactic acid,and increased hormone-sensitive lipase mRNA ***,decreased citrate synthase,isocitrate dehydrogenase alpha,and carnitine palmitoyltransferase 1 mRNA expression were also *** found that AA treatments increased the protein levels of phosphorylated mammalian target of rapamycin(p-mTOR),phosphorylated-p70 ribosomal protein S6 kinase,and phosphorylated-4 E-binding protein *** is more,the protein levels of phosphorylated AMPKα(pAMPKa)and nicotinamide adenine dinucleotide(NAD)-dependent protein deacetylase sirtuin-1(SIRT1)were decreased by AA treatments in a time depending *** bioenergetics and the production of tricarboxylic acid cycle intermediates were decreased upon inhibition of mTORCl or ***,AMPK activation could up-regulate the mRNA expressions of inhibitor of nuclear factor kappa-B kinase subunit beta(Ikbk(3),integrin-linked protein kinase(ILK),unconventional myosin-Ic(Myolc),ribosomal protein S6 kinase beta-2(RPS6 Kβ2),and vascular endothelial growth factor(VEGF)-β,which are downstream effectors of mammalian target of rapamycin(mTOR).The mRNA expressions of phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform(PIK3 CD)and5’-AMP-activated protein kinase subunit gamma-1(PRKAG1),which are upst

关键词： Amino acids Mammalian target of rapamycin Adenosine monophosphate activated protein kinase Mitochondrial respiration Energy utilization

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Analysis of the nitric oxide-cyclic guanosine monophosphate pathway in experimental liver cirrhosis suggests phosphodiesterase-5 as potential target to treat portal hypertension

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World Journal of Gastroenterology 2018年第38期24卷 4356-4368页

作者： Denise Schaffner Adhara Lazaro Peter Deibert Peter Hasselblatt Patrick Stoll Lisa Fauth Manfred W Baumstark Irmgard Merfort Annette Schmitt-Graeff Wolfgang Kreisel Institute for Exercise-und Occupational Medicine Faculty of MedicineUniversity of FreiburgFreiburg 79106Germany Department of Medicine II GastroenterologyHepatologyEndocrinologyand Infectious DiseasesFaculty of MedicineUniversity of FreiburgFreiburg 79106Germany Anaesthesiological Practice Freiburg 79104Germany Institute of Clinical Pathology Faculty of MedicineUniversity of FreiburgFreiburg 79106Germany Department of Pharmaceutical Biology and Biotechnology University of FreiburgFreiburg 79104Germany

AIM To investigate the potential effect of inhibitors of phosphodiesterase-5(PDE-5) for therapy of portal hypertension in liver *** In the rat model of thioacetamide-induced liver fibrosis/cirrhosis the nitric oxide-cyclic guanosine monophosphate(NO-cGMP) pathway was investigated. Expression and localization of PDE-5, the enzyme that converts vasodilating cGMP into inactive 5'-GMP, was in the focus of the study. Hepatic gene expression of key components of the NO-cGMP pathway was determined by qRT-PCR: Endothelial NO synthase(eNOS), inducible NO synthase(iNOS), soluble guanylate cyclase subunits α1 and β1(sGCa1, sGCb1), and PDE-5. Hepatic PDE-5 protein expression and localization were detected by immunohistochemistry. Serum cGMP concentrations were measured using ELISA. Acute effects of the PDE-5 inhibitor Sildenafil(0.1 mg/kg or 1.0 mg/kg) on portal and systemic hemodynamics were investigated using pressure *** Hepatic gene expression of eNOS(2.2-fold; P = 0.003), sGCa1(1.7-fold; P = 0.003), sGCb1(3.0-fold; P = 0.003), and PDE-5(11-fold; P = 0.003) was increased in cirrhotic livers compared to healthy livers. Overexpression of PDE-5(7.7-fold; P = 0.006) was less pronounced in fibrotic livers. iNOS expression was only detected in fibrotic and cirrhotic livers. In healthy liver, PDE-5 protein was localized primarily in zone 3 hepatocytes and to a lesser extent in perisinusoidal cells. This zonation was disturbed in cirrhosis: PDE-5 protein expression in perisinusoidal cells was induced approximately 8-fold. In addition, PDE-5-expressing cells were also found in fibrous septa. Serum cGMP concentrations were reduced in rats with cirrhotic livers by approximately 40%. Inhibition of PDE-5 by Sildenafil caused a significant increase in serum cGMP concentrations [+ 64% in healthy rats(P = 0.024), + 85% in cirrhotic rats(P = 0.018)]. Concomitantly, the portal venous pressure was reduced by 19% in rats with liver cirrhosis. CONCLUSION Overexpres

关键词： Portal hypertension Thioacetamide Nitric oxide Liver cirrhosis Cyclic guanosine monophosphate Phosphodiesterase-5 Sildenafil Hepatic stellate cells Metabolic zonation

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ADSL, AMPD1, and ATIC Expression Levels in Muscle and Their Correlations with Muscle Inosine monophosphate Content in Dapulian and Hybridized Pig Species

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Open Journal of Animal Sciences 2017年第4期7卷 393-404页

作者： Rongsheng Zhu Yanping Wang Huaizhong Wang Song Lin Shouli Sun Baohua Huang Hongmei Hu Institute of Animal Science and Veterinary Medicine Shandong Academy of Agricultural Sciences Jinan China Shandong Key Laboratory of Animal Disease Control and Breeding Jinan China

We investigated the relationship between muscle inosine monophosphate (IMP) content and mRNA levels of ADSL, AMPD1, and ATIC in Dapulian (DPL), Landrace × Dapulian (LDPL), and Duroc × Landrace × Dapulian (DLDPL) hybridized pigs. Methods: The total RNA in longissimus dorsi was isolated from Dapulian (DPL), Landrace × Dapulian (LDPL) and Duroc × Landrace × Dapulian (DLDPL) hybridized pigs, weighed about 95.0 kg, n = 8/species. The internal genes with highest stability (YWHAZ and RPL4) were chosen from 11 common internal genes using Quantitative real-time PCR (qPCR) and geNorm software. The mRNA levels of ADSL, AMPD1 and ATIC genes were corrected with YWHAZ and RPL4 genes. The muscular IMP content was determined by HPLC. The muscular IMP content in DPL was higher than that in LDPL and DLDPL, 25.00% (p 0.05) and 15.56% (p > 0.05), respectively. The muscular mRNA level of ADSL gene in DPL and LDPL was higher than that in DLDPL, 24.14% and 12.07%, respectively (p 0.05). The muscular mRNA level of ATIC gene in DPL and LDPL was higher than that in DLDPL, 66.67% and 33.33%, respectively (p 0.05). The muscular mRNA level of AMPD1 gene in DPL and LDPL was higher than that in DLDPL, 14.49% and 33.26%, respectively. Furthermore, the IMP content was positively correlated with the mRNA level of ADSL, AMPD1 and ATIC genes, respectively (p 0.05). The mRNA level of ADSL gene was highly related to that of AMPD1 and ATIC gene, respectively (p 0.01), while that of AMPD1 gene was not strongly correlated with that of ATIC gene (p > 0.05). The muscular mRNA level of AMPD1, ADSL and ATIC genes and the muscular IMP content in DPL were highest, followed by those in LDPL and DLDPL. The muscular IMP content was positively correlated with the muscular mRNA level of ADSL, AMPD1 and ATIC genes, respectively.

关键词： Pigs ADSL Gene AMPD1 Gene ATIC Gene Correlation Inosine monophosphate

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DETERMINATION OF CYCLIC ADENOSINE monophosphate (cAMP) IN HOMOGENATES OF PARAGONIMUS WORMS

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Chinese Science Bulletin 1983年第6期28卷 832-834页

作者：张夏英钟惠澜熊军曹维霁高佩芝许炽标邵兰 Beijing Tropical Medicine Research Institute

It has long been known that cAMP is the second messenger in the metabolism of mammalians, plants and microbes, so we suppose that cAMP also has some important role in regulating the metabolism of parasites. An investigation on the role of cAMP in regulating the metabolism of parasites seems to have not only theoretical interest, but also practical value in the search for new therapeutic agents for parasitic diseases.

关键词： metabolism regulating microbes parasitic suppose monophosphate messenger adenosine blank hormones

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Absorption of Curcumin monophosphate in Rat Intestinal Circulation

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Medicinal Plant 2019年第1期10卷 66-68,73页

作者： Yu WANG Luyang DING Longru SUN School of Pharmaceutical Science Shandong University

[Objectives] This study aimed to study the absorption of curcumin monophosphate, a derivative of curcumin, in the small intestine of rats. [Methods] In situ recirculation perfusion technique was used to study the absorption of curcumin monophosphate in intestinal circulation of rats, and the content of curcumin monophosphate in intestinal circulation solution was determined by high-performance liquid chromatography/ultraviolet detector(HPLC/UV). [Results] The established HPLC/UV method has good specificity. Linear regression was conducted between the peak area of curcumin monophosphate(A) and the concentration of curcumin monophosphate(C). The established standard curve equation was y=30.07x+102.48(R^2=0.999 0), indicating that curcumin monophosphate has good linearity in the range of 1.25-100.00 μg/mL. After excluding the degradation of the drug and the loss of sampling, within the first 2 h of the experiment, the drug absorption in the small intestine of rat was 1.39 mg, accounting for 97.2% of the total drug absorption during the 5-h experimental period, and the absorption rate was 53.9%.[Conclusions] Curcumin monophosphate has a good absorption in the small intestine of rats.

关键词： Curcumin monophosphate In situ recirculation perfusion Small intestine absorption High performance liquid chromatography

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Symptomatic improvement in an acute, non-traumatic spine pain model with a combination of uridine triphosphate, cytidine monophosphate, and hydroxocobalamin

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Pain Studies and Treatment 2014年第1期2卷 6-10页

作者： Marco Antonio Mibielli Carlos Pereira Nunes Ari Boulanger Scussel Jr. Mendel Suchmacher Neto Lisa Oliveira Mauro Geller Teresópolis Medical School-UNIFESO Rio de Janeiro Brazil

Rationale: In a previously published trial on spinal acute non-traumatic pain, peripheral neuro- regenerative combination of UTP, CMP and hydroxocobalamin presented unexpected analgesicproperties. Objective: To corroborate analgesiceffects of UTP, CMP and hydroxocobalamin combination in a self-paired evolutionary model. Methods: Mean VAS scores from pretreatment, V2 (5th treatment day) and V3 (10th treatment day) were plotted and statistically analyzed (ANOVA) for differences. PFQ scores from pretreatment, V2, and V3 were analyzed using the chisquare test. Results: The difference between V3 and pretreatment mean VAS scores was statistically significant (p < 0.0001). The improvement in PFQ scores throughout the study was found to be statistically significant (p < 0.0001). Conclusion: The combination of UTP, CMP and hydroxocobalamin seems to have analgesic properties in mediumterm use. The complex peripheral neu-roregenerative pharmacodynamics of this combination provides a plausible basis for this finding. Further randomized studies are needed to explore this combination for the indication of neuropathic pain due to spinal structure involvement.

关键词： Uridine Triphosphate Cytidine monophosphate Hydroxocobalamin Analgesia

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Hepatitis C virus core protein induces energy metabolism disorders of hepatocytes by down-regulation of silent mating type information regulation 2 homolog-1 and adenosine monophosphate-acti vated protein kinase signaling pathway

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China Medical Abstracts(Internal Medicine) 2013年第2期30卷 72-72页

作者：于建武 Dept Infect Dis 2nd Affil HospHarbin Med Univ

Objective To study the role of silent mating type information regulation2homotog-1(SIRT1)-adenosine monophosphate(AMP)-activated protein kinase(AMPK) signaling pathway in hepatitis C virus core protein(HCV-core)induce... 详细信息

关键词： monophosphate adenosine metabolism AMPK silent homolog mating signaling cytometry nicotinamide

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Protective effects of inhibition of adenosine monophosphate activated protein kinase activity against cerebral ischemia-reperfusion injury in mice

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China Medical Abstracts(Internal Medicine) 2013年第3期30卷 189-189页

作者：补娟 Dept Neurol People's HospXinjing Uygur Autonom Region

Objective To observe the effect of inhibition of adenosine monophosphate activated protein kinase (AMPK) on shape,function and inflammatory factor of microglia for mice after cerebral

关键词： monophosphate adenosine microglia AMPK occlusion carotid neurological deficit thread interleukin

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Treadmill training improves neurological deficits and suppresses neuronal apoptosis in cerebral ischemic stroke rats

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Neural Regeneration Research 2019年第8期14卷 1387-1393页

作者： Li-Mei Cao Zhi-Qiang Dong Qiang Li Xu Chen Department of Neurology Shanghai No.8 People’s Hospital

RehabilNation training is believed to be beneficial to patients with stroke, but its molecular mechanism is still unclear. Rat models of cerebral ischemic stroke were established by middle cerebral artery occlusion/reperfusion, and then received treadmill training of different intens让ies, twice a day for 30 minutes for 1 week. Low-intensity training was conducted at 5 m/min, with a 10-minute running, 10-minute rest, and 10-minute running cycle. In the moderate-intensity training, the intensity gradually increased from 5 m/min to 10 m/min in 5 minutes, with the same rest cycle as above. In high-intensity training, the intensity gradually increased from 5 m/min to 25 m/min in 5 minutes, with the same rest cycle as above. The Bederson scale was used to evaluate the improvement of motor function. Infarct volume was detected using 2,3,5-triphenyltetrazolium chloride staining. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling staining was applied to detect the apoptosis of nerve cells in brain tissue. Western blot assay was employed to analyze the activation of cyclic adenosine monophosphate (cAMP)/protein kinase A and Akt/glycogen synthase kinase-3卩 signaling pathways in rat brain tissue. All training intensities reduced the neurological deficit score, infarct volume, and apoptosis in nerve cells in brain tissue of stroke rats. Training intensities activated the cAMP/protein kinase A and Akt/glycogen synthase kinase-3 beta signaling pathways. This activation was more obvious with higher training intensities. These changes were reversed by intracerebroventricular injection of protein kinase A inhibitor Rp-cAMP. Our findings indicate that the neuroprotective effect of rehabilitation training is achieved via activation of the cAMP/ protein kinase A and Akt/glycogen synthase kinase-3 beta signaling pathways. This study was approved by the Ethics Committee of Animal Experimentation in Shanghai No. 8 Peoples Hospital, China.

关键词： nerve regeneration ischemic stroke treadmill training neuronal deficit apoptosis cyclic adenosine monophosphate protein kinase A glycogen synthase kinase-3^ neuroprotective effect neural regeneration

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GLYX-13 pretreatment ameliorates long-term isoflurane exposure-induced cognitive impairment in mice

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Neural Regeneration Research 2020年第1期15卷 128-135页

作者： Huan Liu Xiang-Dan Gong Xin Zhao Yue Qian Xiao-Ping Gu Tian-Jiao Xia Department of Anesthesiology The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical SchoolNanjingJiangsu ProvinceChina Jiangsu Key Laboratory of Molecular Medicine Medical School of Nanjing UniversityNanjingJiangsu ProvinceChina

Accumulating evidence indicates that inhalation anesthetics induce or increase the risk of cognitive ***-13(rapastinel)acts on the glycine site of N-methyl-D-aspartate receptors(NMDARs)and has been shown to enhance hippocampus-dependent learning and memory ***,the mechanisms by which GLYX-13 affects learning and memory function are still *** this study,we investigated these mechanisms in a mouse model of long-term anesthesia *** were intravenously administered 1 mg/kg GLYX-13 at 2 hours before isoflurane exposure(1.5%for 6 hours).Cognitive function was assessed using the contextual fear conditioning test and the novel object recognition *** mRNA expression and phosphorylated protein levels of NMDAR pathway components,N-methyl-D-aspartate receptor subunit 2B(NR2B)-Ca^2+/calmodulin dependent protein kinaseⅡ(CaMKII)-cyclic adenosine monophosphate response element binding protein(CREB),in the hippocampus were evaluated by quantitative RT-PCR and western blot *** with GLYX-13 ameliorated isoflurane exposure-induced cognitive impairment and restored NR2B,CaMKII and CREB mRNA and phosphorylated protein *** injection of KN93,a selective CaMKII inhibitor,significantly diminished the effect of GLYX-13 on cognitive function and NR2B,CaMKII and CREB levels in the *** together,our findings suggest that GLYX-13 pretreatment alleviates isoflurane-induced cognitive dysfunction by protecting against perturbation of the NR2B/CaMKII/CREB signaling pathway in the ***,GLYX-13 may have therapeutic potential for the treatment of anesthesia-induced cognitive *** study was approved by the Experimental Animal Ethics Committee of Drum Tower Hospital affiliated to the Medical College of Nanjing University,China(approval No.20171102)on November 20,2017.

关键词： Ca^2+/calmodulin-dependent protein kinaseⅡ cognitive impairment contextual fear conditioning cyclic adenosine monophosphate response element binding protein GLYX-13 isoflurane N-methyl-D-aspartate receptor novel object recognition rapastinel

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