1.Effect of quinacrine on inflammatory reaction of blood system induced by microwave irradiation.
Yan WU ; Zhen-Tao SU ; Hong-Mei ZHOU ; Fei WANG ; Shu-Hong LIU ; Xue-Feng DING ; Yong-Qi ZHAO ; Ming FAN
Journal of Experimental Hematology 2011;19(2):499-502
This work was aimed to investigate the effect of quinacrine on peripheral granulocytes and lymphocytes, interleukin 1 (IL-1) and interleukin 6 (IL-6) in peripheral blood serum of inflammatory reaction induced by microwave irradiation, and observe the protective effect of quinacrine against microwave irradiation injury. BALB/c mice were suffered from microwave irradiation with the total intensity of 50 mW/cm(2) for 30 minutes, at 1 hour before irradiation quinacrine (12.6 mg/kg or 50.4 mg/kg) was orally administrated. Mice received same volume of water for injection instead of quinacrine were named as microwave irradiation group (MR group), and mice received no microwave irradiation but stayed in microwave irradiation environment also for 30 min were set as control. After microwave irradiation, mice were sacrificed and peripheral blood cells were analyzed with cytoanalyzer, and mice serum interleukin-1β, interleukin-6 were detected by radioimmunoassay. The results showed that microwave irradiation increased the count of peripheral granulocytes and lymphocyte along with prolongation of time, while the increase of these cells in mice administrated quinacrine was markedly delayed. The level of IL-1β in serum of mice was significantly increased after 1 day of microwave irradiation (50 mW/cm(2)), and recovered to normal level after 7 days. The 2 concentrations of quinacrine (12.6 mg/kg, 50.4 mg/kg) could suppress level of IL-1β in serum induced by microwave irradiation. The level of IL-6 in serum of mice was gradually increased after microwave irradiation with intensity of 50 mW/cm(2) for 7 days, but quinacrine administration could delay the rise of IL-6 level, specially within time of 2 days. It is concluded that the quinacrine administration can delay the increase of peripheral granulocytes and lymphocytes inducted by microwave irradiation, and may partially suppress the rise of IL-1β and IL-6 in serum. The results of this study suggest that the quinacrine can provide some protective effect against microwave irradiation injury.
Animals
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Inflammation
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Interleukin-1
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blood
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Interleukin-1beta
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blood
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Interleukin-6
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blood
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Leukocyte Count
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Male
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Mice
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Mice, Inbred BALB C
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Microwaves
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adverse effects
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Quinacrine
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pharmacology
2.Protective effect of Quinacrine on striatum neurons from heat treatment injury.
Yong-Qi ZHAO ; Yan WU ; Shu-Hong LIU ; Xue-Ming GE ; Ai-Shi DING ; Ming FAN
Chinese Journal of Applied Physiology 2004;20(4):319-323
AIMTo study the protective effect of Quinacrine(QA) on rat striatum neurons from the injury caused by heat environment treatment, to probe the relationship between cell membrane injury and cellular injury protection, and to seek the possibility of QA as a preventive agent to heat injury.
METHODSPrimary cultured striatum neurons from newborn rats were pretreated with QA at different concentration for 1 h, and then heat-treated at 43 degrees C for another 1 h. Cell necrosis was detected by Trypan blue staining, and apoptosis was evaluated through Activated Caspase-3 dye and TdT dye.
RESULTSHeat treatment effected the survival of striatum neurons and resulted in great number of cell death, which was mainly mediated by cell necrosis process. It was shown that treatment of QA itself had little effect on the survival of striatum neurons, while QA pretreatment decreased cellular necrosis caused by following heat treatment.
CONCLUSIONQA protects striatum neurons from heat environment injury at about 20 pmol/L, and the protection may mediated by reduction of necrosis.
Animals ; Apoptosis ; drug effects ; Caspase 3 ; metabolism ; Cell Death ; drug effects ; Cells, Cultured ; Corpus Striatum ; cytology ; Heat-Shock Response ; Neurons ; drug effects ; Quinacrine ; pharmacology ; Rats ; Rats, Wistar
3.Effects of mastoparan on a vascular contractility in rabbit aorta.
Young Ho LEE ; Sung In KANG ; Duck Sun AHN ; Hye Young LEE ; Eun Jin CHOI ; Bok Soon KANG
Yonsei Medical Journal 1995;36(3):262-270
Mastoparan is an amphiphilic tetradecapeptide derived from wasp venom which activates G-proteins. Several secondary effects have been attributed to this peptide, including activation of phospholipase and phosphatidylinositol kinase. The aim of the present study was to investigate the effects of mastoparan on vascular contractility. Rabbit aortic rings were cut and mounted on a force transducer to record isometric tension on a polygraph. The effects of mastoparan were then investigated on the contractile responses in the isolated rabbit aorta with or without endothelium. The results were summarized as follows; 1. Mastoparan caused biphasic response, a transient relaxation followed by a further contraction, in norepinephrine (NE)-precontracted ring with endothelium. These effects were not observed in the aorta in the absence of endothelium. 2. Mastoparan-induced transient relaxation was significantly inhibited by treatment with a N-omega-nitro-L-arginine or methylene blue. 3. When an inhibitor of phospholipase C, neomycin was added to the precontracted aortic ring with NE, the transient relaxation induced by mastoparan was inhibited, but sustained contraction was not inhibited. 4. When an inhibitor of phospholipase A2, quinacrine and inhibitor of the cyclooxygenase pathway, indomethacin, were added to a precontracted ring with NE, the transient relaxation induced by mastoparan was not inhibited, but sustained contraction was inhibited. 5. Mastoparan induced a contraction of the aorta either with or without endothelium. Indomethacin and nifedipine inhibited mastoparan-induced contraction. From the above results, we concluded that mastoparan acts on the endothelium and modifies the release of endothelium-derived relaxing factors such as nitric oxide and also endothelium-derived contracting factors such as metabolites of arachidonic acid.
Animal
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Aorta/*drug effects/physiology
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Arginine/analogs & derivatives/pharmacology
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Calcium/metabolism
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In Vitro
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Indomethacin/pharmacology
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Neomycin/pharmacology
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Nitroarginine
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Quinacrine/pharmacology
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Rabbits
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Support, Non-U.S. Gov't
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Vasoconstriction/*drug effects
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Wasp Venoms/*pharmacology
4.Prophylactic effect of quinacrine against experimental heatstroke.
Yong-Qi ZHAO ; Lu-Ming WANG ; Cheng XING ; Shu-Hong LIU ; Yan WU ; Ming FAN
Acta Pharmaceutica Sinica 2007;42(8):817-821
The present study is to assess the prophylactic effect of quinacrine (QA) , an anti-malarial drug, against heatstroke in rats. Conscious rats were orally given equal volume normal saline or QA (dissolved in normal saline and final dosage for rats was 4.5, 9.0 and 18 mg x kg(-1)). An hour later rats were put into a warm water circulated hot chamber (41.0 +/- 0.5) degrees C. Rectal temperature (core temperature, T(co)) of rats in hot chamber was continuously monitored by a thermocouple. T(co) and survival time of rats showed that QA pre-treatment postponed the hyperthermia, and increased the survival time of rats in hot chamber. Primary striatum neurons' culture from new born rats was maintained with D-MEM and 10% FBS. After immuno-cytochemistry identification with antibodies against neural specific proteins, culture received 20 micromol x L(-1) QA only for 1 h and followed by 43.0 degrees C heat treatment for another hour, or 20 micromol x L(-1) QA for 1 h followed by 43.0 degrees C heat treatment for another hour. Control culture received heat treatment only. Cultures were labeled with the fluorescent indicator DPH and the relative membrane fluidity of neurons was measured with the help of fluorescent polarized spectrophotometer. [3H] Arachidonic acid (AA) labeled membrane of E. Coli cells was used as substrate to determine cPLA2 activity of neurons. Gas chromatography and mass spectrum were also employed to detect on the level of fatty acids level in rat striatum neurons. Results from cells indicated that inhibition of cPLA2, reduction the release of active fatty acids such as AA, and possibly, stabilization of the cell membrane which was disturbed by hot treatment, may contribute to the mechanism underlying heat protection and heatstroke preventive effects of quinacrine.
Animals
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Cells, Cultured
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Corpus Striatum
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drug effects
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pathology
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Fatty Acids
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metabolism
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Heat Stroke
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metabolism
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physiopathology
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prevention & control
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Hot Temperature
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adverse effects
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Male
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Membrane Fluidity
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drug effects
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Neurons
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enzymology
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metabolism
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physiology
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Phospholipases A2
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metabolism
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Quinacrine
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pharmacology
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Rats
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Rats, Wistar
5.STAT3 is involved in phosphatidic acid-induced Bcl-2 expression in HeLa cells.
Hye Jin CHOI ; Jung Han LEE ; Shin Young PARK ; Ju Hwan CHO ; Joong Soo HAN
Experimental & Molecular Medicine 2009;41(2):94-101
Phosphatidic acid (PA), the product of a PLD-mediated reaction, is a lipid second messenger that participates in various intracellular signaling events and is known to regulate a growing list of signaling proteins. We found that Bcl-2 was upregulated by PA treatment in HeLa cells. However, how PA upregulates Bcl-2 expression has not yet been studied. In this study, we tried to discover the mechanisms of Bcl-2 up-regulation by PA treatment in HeLa cells. Treatment with PA resulted in significantly increased expression of Bcl-2 in HeLa cells. Moreover, PA-induced Bcl-2 expression was blocked by mepacrine, an inhibitor of PLA2, but not by propranolol, an inhibitor of PA phospholyhydrolase (PAP). Treatment of 1,2-dipalmitoryl-sn-glycero-3-phosphate (DPPA) also increased Bcl-2 expression. These results indicate that Bcl-2 expression is mediated by lysophosphatidic acid (LPA), not by arachidonic acid (AA). Thereafter, we used MEK1/2 inhibitor, PD98059 to investigate the relationship between ERK1/2 MAPK and PA-induced Bcl-2 expression. PA-induced Bcl-2 expression was decreased when ERK1/2 was inhibited by PD98059. The transcription factor such as STAT3 which is controlled by ERK1/2 MAPK was increased along with Bcl-2 expression when the cells were treated with PA. Furthermore, STAT3 siRNA treatments inhibited PA-induced Bcl-2 expression, suggesting that STAT3 (Ser727) is involved in PA-induced Bcl-2 expression. Taken together, these findings indicate that PA acts as an important mediator for increasing Bcl-2 expression through STAT3 (Ser727) activation via the ERK1/2 MAPK pathway.
Enzyme Inhibitors/pharmacology
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Gene Expression Regulation, Neoplastic
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Hela Cells
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Humans
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Mitogen-Activated Protein Kinase Kinases/genetics/metabolism
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Phosphatidic Acids/*genetics/metabolism
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Propranolol/pharmacology
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Proto-Oncogene Proteins c-bcl-2/*genetics/metabolism
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Quinacrine/pharmacology
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RNA, Small Interfering/genetics
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STAT3 Transcription Factor/*genetics/metabolism