1.Effects between the first-and second-generation histamine H1-antagonists on seizure development of pentylenetetrazole-induced kindling in rats.
Chun-lei JIN ; Zhong CHEN ; Li-san ZHANG ; Yi GUO ; Liu-yan ZHANG ; Kazuhiko YANAI
Journal of Zhejiang University. Medical sciences 2004;33(3):209-212
OBJECTIVETo investigate the effects and the mechanisms of the first-generation histamine H(1)-antagonist diphenhydramine and the second-generation histamine H(1)- antagonist fexofenadine on seizure development of pentylenetetrazole (PTZ)-induced kindling in rats.
METHODSThe first-or second-generation histamine H(1)-antagonists and/or histidine were ip injected in rats every 48 h, followed by a subconvulsive dose of PTZ (35 mg/kg). Then the behavioral changes were observed for 30 min after every injection of PTZ. The histamine content of brain was measured spectrofluorometrically.
RESULTCompared with the control group, diphenhydramine (5 mg/kg) significantly augmented the severity of seizure development of PTZ-induced kindling, whereas fexofenadine (5 mg/kg) had no marked influence. The effects of diphenhydramine were antagonized by histidine, the precursor of histamine.
CONCLUSIONSeizure development of PTZ-induced kindling is promoted by the first-but not the second generation histamine H(1)-antagonists via the blockade of brain histamine H(1)-receptor.
Animals ; Histamine ; physiology ; Histamine H1 Antagonists ; pharmacology ; Histamine H1 Antagonists, Non-Sedating ; pharmacology ; Histidine ; pharmacology ; Kindling, Neurologic ; drug effects ; Male ; Pentylenetetrazole ; Rats ; Rats, Sprague-Dawley ; Seizures ; chemically induced
2.Mechanisms of the effect of brain histamine on chronic epilepsy induced by pentylenetetrazole.
Li-san ZHANG ; Hai-qing SHEN ; Chun-lei JIN ; Wei-wei HU ; Meng-hui ZHAO ; Zhong CHEN
Journal of Zhejiang University. Medical sciences 2004;33(3):201-204
OBJECTIVETo investigate the mechanisms of histamine on chronic epilepsy induced by pentylenetetrazole (PTZ).
METHODSTo induce chemical kindling, a subconvulsive dose (35mg/kg) of PTZ was ip injected every 48 h in rats. Behavior changes were observed for 30 min after every injection of PTZ.
RESULTIp injection of histidine or icv injection of clobenpropit inhibited the development of kindling induced by PTZ, presenting prolonged latency for myoclonic jerks and clonic generalized seizures and depressed seizure stages in a dose-dependent manner. H(3)receptor agonist, immepip, and histidine decarboxylase, alpha-fluoromethylhistidine reversed the ameliorating effect of clobenpropit on seizure development in a dose-dependent manner.
CONCLUSIONBrain histamine plays an important role in protection against myoclonic jerks and clonic generalized clonic seizures and its action may be via H(3)receptor.
Animals ; Brain ; physiology ; Chronic Disease ; Dose-Response Relationship, Drug ; Epilepsy ; chemically induced ; Histamine ; physiology ; Histidine ; pharmacology ; Imidazoles ; pharmacology ; Male ; Pentylenetetrazole ; pharmacology ; Piperidines ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Thiourea ; analogs & derivatives ; pharmacology
3.RGFP966 inactivation of the YAP pathway attenuates cardiac dysfunction induced by prolonged hypothermic preservation.
Xiao-He ZHENG ; Lin-Lin WANG ; Ming-Zhi ZHENG ; Jin-Jie ZHONG ; Ying-Ying CHEN ; Yue-Liang SHEN
Journal of Zhejiang University. Science. B 2020;21(9):703-715
Oxidative stress and apoptosis are the key factors that limit the hypothermic preservation time of donor hearts to within 4-6 h. The aim of this study was to investigate whether the histone deacetylase 3 (HDAC3) inhibitor RGFP966 could protect against cardiac injury induced by prolonged hypothermic preservation. Rat hearts were hypothermically preserved in Celsior solution with or without RGFP966 for 12 h followed by 60 min of reperfusion. Hemodynamic parameters during reperfusion were evaluated. The expression and phosphorylation levels of mammalian STE20-like kinase-1 (Mst1) and Yes-associated protein (YAP) were determined by western blotting. Cell apoptosis was measured by the terminal deoxynucleotidyl-transferase (TdT)-mediated dUTP nick-end labeling (TUNEL) method. Addition of RGFP966 in Celsior solution significantly inhibited cardiac dysfunction induced by hypothermic preservation. RGFP966 inhibited the hypothermic preservation-induced increase of the phosphorylated (p)-Mst1/Mst1 and p-YAP/YAP ratios, prevented a reduction in total YAP protein expression, and increased the nuclear YAP protein level. Verteporfin (VP), a small molecular inhibitor of YAP-transcriptional enhanced associate domain (TEAD) interaction, partially abolished the protective effect of RGFP966 on cardiac function, and reduced lactate dehydrogenase activity and malondialdehyde content. RGFP966 increased superoxide dismutase, catalase, and glutathione peroxidase gene and protein expression, which was abolished by VP. RGFP966 inhibited hypothermic preservation-induced overexpression of B-cell lymphoma protein 2 (Bcl-2)-associated X (Bax) and cleaved caspase-3, increased Bcl-2 mRNA and protein expression, and reduced cardiomyocyte apoptosis. The antioxidant and anti-apoptotic effects of RGFP966 were cancelled by VP. The results suggest that supplementation of Celsior solution with RGFP966 attenuated prolonged hypothermic preservation-induced cardiac dysfunction. The mechanism may involve inhibition of oxidative stress and apoptosis via inactivation of the YAP pathway.
Acrylamides/pharmacology*
;
Animals
;
Apoptosis/drug effects*
;
Cryopreservation
;
Disaccharides/pharmacology*
;
Electrolytes/pharmacology*
;
Glutamates/pharmacology*
;
Glutathione/pharmacology*
;
Heart/physiology*
;
Heart Transplantation/methods*
;
Hepatocyte Growth Factor/antagonists & inhibitors*
;
Histidine/pharmacology*
;
Histone Deacetylase Inhibitors/pharmacology*
;
Intracellular Signaling Peptides and Proteins/antagonists & inhibitors*
;
Male
;
Mannitol/pharmacology*
;
Oxidative Stress/drug effects*
;
Phenylenediamines/pharmacology*
;
Proto-Oncogene Proteins/antagonists & inhibitors*
;
Rats
;
Rats, Sprague-Dawley
;
Signal Transduction/drug effects*
;
YAP-Signaling Proteins
4.Effects of clobenpropit and histidine on reinstatement of morphine-induced conditioned place preference.
Hui-Juan WANG ; Min LU ; Ying-Xia GONG ; Zhong CHEN
Journal of Zhejiang University. Medical sciences 2009;38(6):559-564
OBJECTIVETo investigate the effects of clobenpropit and histidine on reinstatement of morphine-induced conditioned place preference (CPP) in rats.
METHODSThe persistence, extinction and reinstatement of morphine-induced CPP were established.In clobenpropit group three different doses of clobenpropit (2, 5 and 10 microg/rat, i.c.v.) were administered 15 min after morphine (1 mg/kg, i.p.) was injected. In histidine group histidine (100, 200, 500 mg/kg) was given 1 h prior to morphine treatment (1 mg/kg i.p).
RESULTThe CPP was reinstated by priming injection of 1 mg/kg morphine. Clobenpropit (5, 10 microg/rat) significantly inhabited the reinstatement by a priming dose of morphine-induced CPP compared with the morphine control group; histidine (100, 200, 500 mg/kg) significantly inhibited the reinstatement in a dose-dependent manner.
CONCLUSIONClobenpropit and histidine inhibit the revival of morphine-induced CPP in a dose dependent manner, indicating that endogenous histamine may inhibit relapse of morphine to some extent.
Animals ; Conditioning, Operant ; drug effects ; Histidine ; metabolism ; Imidazoles ; pharmacology ; Male ; Morphine Dependence ; physiopathology ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Receptors, Cell Surface ; antagonists & inhibitors ; Substance Withdrawal Syndrome ; physiopathology ; Thiourea ; analogs & derivatives ; pharmacology
5.Mechanisms of histamine ameliorating memory impairment induced by pentylenetetrazole-kindling epilepsy in rats.
Lisan ZHANG ; Guanfeng CHEN ; Jiefang CHEN ; Xudong HE ; Xingyue HU
Journal of Zhejiang University. Medical sciences 2017;46(1):1-6
To investigate the effects of neuronal histamine on spatial memory acquisition impairment in rats with pentylenetetrazole-kindling epilepsy, and to explore its mechanisms.A subconvulsive dose of pentylenetetrazole (35 mg/kg) was intraperitoneally injected in rats every 48 h to induce chemical kindling until fully kindled. Morris water maze was used to measure the spatial memory acquisition of the rats one week after fully pentylenetetrazole-kindled, and the histamine contents in different brain areas were measured spectrofluorometrically. Different dosages of hitidine (the precursor of histamine), pyrilamine (H1 receptor antagonist), and zolantidine (H2 receptor antagonist) were intraperitoneally injected, and their effects on spatial memory acquisition of the rats were observed.Compared with control group, escape latencies were significantly prolonged on Morris water maze training day 2 and day 3 in pentylenetetrazole-kindling epilepsy rats (all<0.05); and the histamine contents in hippocampus, thalamus and hypothalamus were decreased significantly (all<0.05). Escape latencies were markedly shortened on day 3 by intraperitoneally injected with histidine 500 mg/kg, and on day 2 and day 3 by intraperitoneally injected with histidine 1000 mg/kg in pentylenetetrazole-kindling epilepsy rats (all<0.05). The protection of histidine was reversed by zolantidine (10 and 20 mg/kg), but not by pyrilamine.Neuronal histamine can improve the spatial memory acquisition impairment in rats with pentylenetetrazole-kindling epilepsy, and the activation of H2 receptors is possibly involved in the protective effects of histamine.
Animals
;
Benzothiazoles
;
pharmacology
;
Brain Chemistry
;
drug effects
;
Epilepsy
;
chemically induced
;
complications
;
Hippocampus
;
chemistry
;
Histamine H1 Antagonists
;
pharmacology
;
Histamine H2 Antagonists
;
pharmacology
;
Histidine
;
pharmacology
;
Hypothalamus
;
chemistry
;
Kindling, Neurologic
;
physiology
;
Memory Disorders
;
drug therapy
;
etiology
;
Pentylenetetrazole
;
Phenoxypropanolamines
;
pharmacology
;
Piperidines
;
pharmacology
;
Pyrilamine
;
pharmacology
;
Rats
;
Rats, Sprague-Dawley
;
Receptors, Histamine H2
;
drug effects
;
physiology
;
Spatial Memory
;
drug effects
;
Spectrometry, Fluorescence
;
Thalamus
;
chemistry
6.Expression of recombinant human beta-defensin-2 gene with C terminal of double marks of Myc and poly-histidine in transfected COS-7 cells.
Shaohui CAI ; Jun DU ; Xinnian CHENG ; Ning HUANG ; Nagase FUMIHIKO ; Hasegawa TAKAIKI ; Boyao WANG
Journal of Biomedical Engineering 2003;20(2):255-280
The aim of this study is to explore the possibility and technical itinerary of establishing an mammal engineering cell line in which hBD-2 can be effectively expressed, secreted, detected, separated and purified. The full hBD2 cDNA was inserted into the multi clone site of a eukaryotic expressive plasmid pcDNA3.1/Myc-His(+) and located closely at the upstream of two tag gene (myc and 6 Poly-histidines) so as to construct another recombinant eukaryotic expressive vector of hBD-2 gene: rpcDNA3.1/Myc-His/hBD-2. By the use of RT-PCR with special primers, a band of 240 bp was amplified from COS-7 cells transfected by this recombinant plasmid, which matched full length of cDNA coding hBD2 plus myc epitope and 6 poly-histidines tags. Western blot analysis with specific anti-histidines antibody revealed that the lysate of COS-7 cells transfected by rpcDNA3.1/Myc-His/hBD-2 had a strong band with molecular weight of about 10 Kd that was approximate to the size of chiasmic peptide. Antibacterial activity assay showed that obvious bacterial inhibition occurred in both lysate and supernatant of COS-7 cells transfected by rpcDNA3.1/Myc-His/hBD-2.
Animals
;
Base Sequence
;
Blotting, Western
;
COS Cells
;
Gene Expression
;
Genes, myc
;
Histidine
;
genetics
;
Humans
;
Molecular Sequence Data
;
Plasmids
;
Reverse Transcriptase Polymerase Chain Reaction
;
Transfection
;
beta-Defensins
;
biosynthesis
;
genetics
;
pharmacology
7.Involvement of endogenous histamine in modulatory effect of morphine on seizure susceptibility in mice.
Zheng-Bing ZHU-GE ; Yuan-Yuan ZHU ; Deng-Chang WU ; Chun-Lei JIN ; Zhong CHEN
Journal of Zhejiang University. Medical sciences 2007;36(2):130-154
OBJECTIVETo investigate the modulatory effects of morphine on the susceptibility to pentylenetetrazole-induced seizures, and the involvement of endogenous histamine in this process.
METHODSBoth the wild-type (WT) mice and histidine decarboxylase (a key enzyme for histamine biosynthesis) deficient (HDC-KO) mice were subcutaneously injected with different doses of morphine, and 1 hour later the pentylenetetrazole solution (1.5 %) was infused into the tail vein at a constant rate of 0.3 ml/min. The minimal dose of pentylenetetrazole (mg/kg) needed to induce myoclonic jerks and clonus convulsion was recorded as the thresholds of seizures.
RESULTIn WT mice, morphine dose-dependently decreased the thresholds of both myoclonic jerks and clonus convulsion. In HDC-KO mice, morphine at 10 mg/kg only significantly decreased the threshold of myoclonic jerks from (38.6 +/-2.9)mg/kg to (32.5 +/-0.7)mg/kg, but had no significant effect on the threshold of clonus convulsion [from (51.8 +/-2.1)mg/kg to (47.6 +/-1.2)mg/kg]. In addition, the value of decreased myoclonic jerks (15.8 +/-1.4)% and clonus convulsion (8.3 +/-0.9)% thresholds were much lower in HDC-KO mice than in WT mice [(26.1 +/-2.5)% and (20.8 +/-2.4)%, respectively].
CONCLUSIONMorphine can decrease the thresholds of pentylenetetrazole in induction of seizure, and the endogenous histamine may be involved in this process.
Animals ; Disease Susceptibility ; chemically induced ; metabolism ; physiopathology ; Dose-Response Relationship, Drug ; Histamine ; metabolism ; physiology ; Histidine Decarboxylase ; genetics ; metabolism ; Male ; Mice ; Mice, Knockout ; Morphine ; pharmacology ; Myoclonus ; chemically induced ; metabolism ; physiopathology ; Narcotics ; pharmacology ; Pentylenetetrazole ; Random Allocation ; Seizures ; chemically induced ; genetics ; physiopathology ; Sensory Thresholds ; drug effects
8.hNUDT16: a universal decapping enzyme for small nucleolar RNA and cytoplasmic mRNA.
Guangwen LU ; Jie ZHANG ; Yan LI ; Zhixin LI ; Na ZHANG ; Xiang XU ; Tingting WANG ; Zhenhong GUAN ; George F GAO ; Jinghua YAN
Protein & Cell 2011;2(1):64-73
Human NUDT16 (hNUDT16) is a decapping enzyme initially identified as the human homolog to the Xenopus laevis X29. As a metalloenzyme, hNUDT16 relies on divalent cations for its cap-hydrolysis activity to remove m⁷GDP and m²²⁷GDP from RNAs. Metal also determines substrate specificity of the enzyme. So far, only U8 small nucleolar RNA (snoRNA) has been identified as the substrate of hNUDT16 in the presence of Mg²(+). Here we demonstrate that besides U8, hNUDT16 can also actively cleave the m⁷GDP cap from mRNAs in the presence of Mg²(+) or Mn²(+). We further show that hNUDT16 does not preferentially recognize U8 or mRNA substrates by our cross-inhibition and quantitative decapping assays. In addition, our mutagenesis analysis identifies several key residues involved in hydrolysis and confirms the key role of the REXXEE motif in catalysis. Finally an investigation into the subcellular localization of hNUDT16 revealed its abundance in both cytoplasm and nucleus. These findings extend the substrate spectrum of hNUDT16 beyond snoRNAs to also include mRNA, demonstrating the pleiotropic decapping activity of hNUDT16.
Amino Acid Motifs
;
Biocatalysis
;
Cell Nucleus
;
enzymology
;
Consensus Sequence
;
Cytoplasm
;
enzymology
;
metabolism
;
Guanosine Diphosphate
;
metabolism
;
Histidine
;
metabolism
;
Humans
;
Hydrolysis
;
Luciferases
;
genetics
;
Magnesium
;
metabolism
;
Manganese
;
metabolism
;
Mutagenesis
;
Mutation
;
Pyrophosphatases
;
antagonists & inhibitors
;
chemistry
;
genetics
;
metabolism
;
RNA Caps
;
chemistry
;
metabolism
;
pharmacology
;
RNA, Small Nucleolar
;
chemistry
;
metabolism
;
pharmacology