摘要
苦马豆素因具有较强的细胞毒、免疫调节、细胞保护、抗病毒和抑菌作用,能抑制肿瘤转移、扩散,促细胞凋亡,近年备受国内外学者的关注。研究认为,苦马豆素对多种α-甘露糖苷酶具有抑制作用,对哪种α-甘露糖苷酶的抑制起主导作用还不得而知,是否对α-甘露糖苷酶转录、翻译、加工修饰产生影响还不清楚。本研究以含苦马豆素的甘肃棘豆(Oxytropis kansuensis Bunge)为毒源,用SD大鼠复制苦马豆素中毒模型,通过生化指标、抗氧化指标、病理组织学和分子生物学等研究,探讨苦马豆素对SD大鼠亚急性毒性及α-甘露糖苷酶在mRNA水平的影响;通过免疫组织化学方法,研究高尔基体α-甘露糖苷酶Ⅱ在SD大鼠不同组织的分布,以及SD大鼠甘肃棘豆亚急性中毒时高尔基体α-甘露糖苷酶Ⅱ在不同组织中的蛋白表达情况。研究取得以下结果:
1. SD大鼠甘肃棘豆亚急性中毒模型复制64只SD大鼠随机分为4组,即对照组、试验Ⅰ组、试验Ⅱ组、试验Ⅲ组。将甘肃棘豆全草粉碎后,按Ⅰ组添加15%(含苦马豆素0.03‰)、Ⅱ组添加30%(含苦马豆素0.06‰)、Ⅲ组添加45%(含苦马豆素0.09‰)的比例制作混合饲料,饲喂至77天试验Ⅲ组出现疯草中毒临床典型症状。
2.甘肃棘豆对SD大鼠血液学指标和生化指标的影响试验结果显示,SD大鼠发生甘肃棘豆亚急性中毒后,RBC、MCV、RDW均降低;GLU、CR、BUN、ALB、TG、ALT变化存在剂量、时间效应,与对照组比较差异显著或差异极显著(P<0.05或P<0.01),并随攻毒时间的延长逐渐升高。
3.甘肃棘豆对SD大鼠抗氧化指标的影响甘肃棘豆能使血清中SOD活力和MDA含量下降,CAT活力先升高后降低。试验组大鼠大脑、肝脏、肾脏、脾脏组织SOD活力在试验初期都有升高趋势,但高剂量组在试验后期受到抑制。大脑组织中CAT含量随攻毒剂量和时间先降低后升高,低剂量甘肃棘豆能使肝脏CAT活力升高。试验组肝脏组织MDA含量在第35天与对照组差异极显著,试验后期低剂量组肾脏组织中MDA含量明显升高。
4.甘肃棘豆对SD大鼠的病理学影响SD大鼠甘肃棘豆中毒能引起脑组织中部分神经细胞周围出现较大空隙,且HE染色变淡。小脑中浦肯野细胞、脑干网状结构、肾脏、肝脏、脾脏出现以空泡变性为特征的病理变化,肾脏远曲小管病理变化要严重于近曲小管,脾脏边缘区出现大量巨噬细胞。
5.甘肃棘豆对SD大鼠α-甘露糖苷酶mRMA表达的影响甘肃棘豆能引起大脑和肾脏MAN2A1 mRNA表达水平的下降,但与对照组比较对大脑影响差异不显著(P>0.05);低剂量甘肃棘豆对肝脏中MAN2A1 mRNA表达具有抑制作用,差异极显著(P<0.01);脾脏结果与肾脏相反,但差异不显著(P>0.05)。大脑、肝脏、肾脏、脾脏的MAN2BA mRNA表达均下降,大脑和脾脏表达差异不显著(P>0.05),肝脏表达差异极显著(P<0.01),肾脏高剂量组差异显著(P<0.05)。
6.甘肃棘豆对SD大鼠MAN2A1分布与表达的影响MAN2A1在脑组织中除大脑分子层、海马辐射层,海马始层,齿状回分子层不表达外,其它区域均有分布,表达量与神经细胞和颗粒细胞的数量正相关,这两种细胞的MAN2A1表达量明显高于其他类型的细胞。肾脏集合小管和远曲小管直部MAN2A1表达相对较强,肝脏和脾脏组织种细胞类型较少,分布差异不明显。试验组大脑、小脑、肾脏中MAN2A1表达量随攻毒剂量增加而降低,浦肯野细胞层部分细胞MAN2A1表达消失,肝脏组织在低剂量甘肃棘豆作用下MAN2A1表达就会受到明显抑制。
It has been documented that SW has such functions as cytotoxicity, immunoregulation, cytoprotection, antiviral and antibacterial activities etc, which enables it to inhibite the metastasis and the spread of the tumor cells while to stimulate the apoptosis, which makes many researchers focus on it. It has been described that SW is an efficient and specific inhibitor of different kinds ofα-mannosidases, but which is inhibited most is not known. It is also not clear that whether SW has effects on the transcription, translation, processing and modification ofα-mannosidase. In this research, SW poisoning model was reconstructed in SD rats using Oxytropis kansuensis Bunge as the SW resourse, through the monitor of biochemical and antioxidant indexes and the histopathological and molecular biological researches, the subacute toxicity of SW towards SD rats and its effects on MAN2A1 and MAN2B1 at mRNA level were investigated. Furthermore the distribution and expression of MAN2A1 in different tissues of SD rats during the subacute O. kansuensis Bunge intoxication were investigated through immunohistochemical assay. The results are as below:
1. Reconstruction of subacute O. kansuensis Bunge poisoning model in SD rats
64 SD rats were divided into 4 groups (the control group and experimental groupⅠ,Ⅱ,Ⅲ), the dried plant of the Oxytropis kansuensis Bunge was comminuted, and different amounts of the grass powder (15%, 30% and 45% respectively, and the corresponding SW content was 0.03‰, 0.06‰, 0.09‰) were mixed with the feeds for the three experimental groups. After 77 days, The experimental groupⅢshowed typical clinical symptoms of loco disease.
2. Effects of O. kansuensis Bunge on the hematologic and biochemical indicators in SD rats
The results indicated that, after the poisoning, the values of RBC, MCV, RDW decreased. A time-effect as well as a dose-effect relationship was observed in GLU, CR, BUN, ALB, TG and ALT, and there was significant difference or extremely significant difference compared with the control group (P<0.05 or P<0.01), moreover the values increased with the experimental time extention.
3. Effects of O. kansuensis Bunge on antioxidant indexes in SD rats
It was observed that the levels of serum SOD and MDA reduced in SD rats after intaking O. kansuensis Bunge, while the CAT activity increased at first and then decreased. The SOD activity in the all four tissues of Experiment Groups rose in the initial stage, which decreased in the later stage in high-dose group. The CAT activity decreased at first and then increased with dose of intaking O. kansuensis Bunge rose and time extension in cerebrum, and livers’increased in Low-dose group. The difference of livers’MDA content was extremely significant between the Experiment Groups and the Control Group at the 35th day, and the kidneys’increased significantly in the later stage in Low-dose group.
4. The pathological effects of O. kansuensis Bunge on SD rats
During the intoxication, there were comparatively large interspaces round the nerve cells in the Thalamus, Hypothalamus and Midbrain etc, which was dyed lighter compared with the normal ones by H-E staining. Purkinje cells, brainstem reticular formation, kidneys, liver and spleen appeared pathological changes with characterized vacuolar degeneration. the pathological changes in proximal convoluted tubule were more serious than thoses in distal convoluted tubule, moreover there were large amount of macrophagocytes in the splenic marginal zone.
5. Effects of O. kansuensis Bunge on the expression ofα-mannosidase mRMA in SD rats
O. kansuensis Bunge inhibited the expression of cerebral and renal MAN2A1 mRNA, but the difference was not obvious in cerebrum (P>0.05). Low-dose O. kansuensis Bunge inhibited the expression of hepatic MAN2A1 mRNA while the high-dose one promoted it and the difference was extremely significant (P<0.01), which was opposite with that of spleen’s, but the difference was not obvious in spleen (P>0.05). The expression of MAN2B1 mRNA decreased in the all four tissues, and the differences were not remarkable in cerebrum and spleen (P>0.05), whereras it was extremely significant in liver(P<0.01), and there was obvious difference in the kidneys in high-dose group (P<0.05).
6. Effects of O. kansuensis Bunge on the distribution and expression of MAN2A1 in SD rats
It was found that MAN2A1 expressed in all the areas but the cerebral molecular layer, Rad, Or and Mol in brain. The expression level of MAN2A1 positively correlated with the amount of the nerve cells and the granulocytes, in which MAN2A1 expressed more than other cells. The expression level of MAN2A1 was relatively higher in collecting tubule and distal convoluted tubule in kidneys, while there were no remarkable differences in hepatic and the splenic tissue. Moreover the expression level of MAN2A1 decreased with the increase of the poisonous dosage in cerebrum, cerebellum and kidneys, and the expression in some purkinje cells disappeared, which was inhibited significantly in liver in the Low-dose group.
引文
阿翰林,党生贵,张生武,张守相. 1994.刚察县哈尔盖乡甘肃棘豆调查与灭治.青海畜牧兽医杂志,24(1): 5~7
百度百科. 2011.甘露糖苷过多症. http://baike.baidu.com/view/4367533.htm[2011-04-05]
曹光荣,李绍君,段得贤,赵效文, Molyneux R J. 1989.黄花棘豆有毒成分的分离与鉴定.西北农业大学学报, 17(3): 1~7
陈德坤,雷莉辉,郭战军,王文秀. 2003.甘肃棘豆生物碱对小鼠外周血免疫细胞活性及数量的影响.中国兽医科技, 33(5): 34-36
陈绍淑,赵宝玉,何生虎,谭承建,董强. 2004.小鼠小花棘豆生物碱中毒的病理学观察.中国兽医科技, 34(12): 77~79
崔友文. 1959.中国北部和西北部重要饲料植物和毒害植物.北京:高等教育出版社
丁伯良. 1993.甘肃棘豆引起母羊流产和公羊不育的机理研究. [博士学位论文].陕西杨凌:西北农林科技大学
丁伯良,王建辰,薛登民,王淑娥. 1994a.甘肃棘豆及中毒奶山羊尿液、胎水、胎儿胎盘中苦马豆素的检验.草地学报, 2(2): 67~63
丁伯良,王建辰,薛登民,贾维真,王淑娥,马远莉. 1994b.山羊甘肃棘豆中毒睾丸、附睾的病理学研究.畜牧兽医学报, 25(04): 367~374
丁伯良,王建辰. 1994c.甘肃棘豆对山羊精子形态和超微结构的影响.西北农业大学学报, 22(02): 44~49
丁伯良,王建辰,薛登民,贾维真,王淑娥. 1995.奶山羊甘肃棘豆中毒卵巢、胎盘的病理学研究.中国兽医学报, 15(1): 27~32
耿果霞,李勤凡,王建华. 1999.山羊冰川棘豆中毒的血清蛋白分析.西北农业大学学报, 27(5): 71~74
耿晓修,丁诗华,孙翰昌,廖品福,张涛. 2006.六价铬对草鱼肝脏SOD和GSH-Px活力的影响.西南农业大学学报, 28(2): 332~336
顾百群,段得贤,崔中林,曹光荣. 1990.山羊甘肃棘豆中毒临床病理学研究.西北农业大学学报, 18(3): 62~68
郭定宗. 2006.兽医临床检验技术.北京:化学工业出版社
霍红雁,卢萍,牛艳芳,吕桂芬,李松,高静,钱亚光. 2010.小花棘豆(Oxytropis glabra DC.)11株内生真菌的分离培养及鉴定.内蒙古大学学报(自然科学版), 41(02): 206~211
吉林农业大学畜牧兽医系编. 1978.家畜中毒.长春:吉林农业大学畜牧兽医系
贾慧娟,李渊,武娟娟,张安民. 2010.运动与海马cAMP的研究进展.搏击(体育论坛), 29(1): 25~29
李建科,卢健雄,杨具田,刘诩中,王英东,何佩. 1996.甘肃棘豆饲喂小白鼠的亚慢性毒性试验的血液学分析.中兽医医药杂志, (3): 6~9
李勤凡,王建华,谭远友,齐雪茹,耿果霞. 2000.奶山羊冰川棘豆中毒的血液生化指标研究.西北农业学报, 9(4): 40~42
李勤凡,王建华,耿果霞,闫小兵,王筱婷. 2004.冰川棘豆对家兔的毒性研究.畜牧兽医学报, 35(6):716~719
李勤凡. 2005.冰川棘豆毒素的毒性及细菌降解研究. [博士学位论文].陕西杨凌:西北农林科技大学
梁建成,邓树嵩,马迎教,李韬. 2011.铅对小鼠肝脏超氧化物歧化酶活性及CuZn- SOD mRNA表达的影响.现代预防医学, 38(7): 1220~1222
刘红霞,苏卫,张连峰. 2006.α-甘露糖苷酶研究进展.中国比较医学杂志, 16(11): 697~720
刘凌,庞缨,叶絮,冯莹. 2010. 121例血小板减少症病因分析.广东医学, 30(4): 453-455
刘胜,周文华, Gary A. 2010.可卡因戒断后的奖赏改变与下丘脑外侧区食欲素表达.中国临床药理学与治疗学, 15(9): 986~990
刘忠艳,赵宝玉,孙莉莎,万学攀,霍星华. 2008.苦马豆素来源及其检测方法的研究进展.中国兽医科学, (02): 1752~180
刘宗平. 2008.兽医临床症状鉴别诊断学.北京:中国农业出版社
卢萍, Dennis C,赵萌莉, Dale R G,吕桂芬,韩国栋. 2009.小花棘豆(Oxytropis glabra DC.)内生真菌的培养与鉴定.生态学报29(01): 53~58
卢围,路浩,赵宝玉,荣杰,陈基萍,王瑞,高文超,陈占莉. 2011.小花棘豆产苦马豆素内生真菌的筛选与鉴定.畜牧兽医学报, 42(3): 429~436
路浩,王建军,孙莉莎,赵宝玉,王占新,马尧,陈基萍,刘忠艳. 2009.苦马豆素抗肿瘤作用研究进展.动物医学进展, 30(09): 87~90
路浩,孙莉莎,赵宝玉,王占新,刘忠艳,郭翀宇,马尧. 2010.哈密黄芪对小鼠的亚急性毒性试验.中国兽医学报, 30(07): 982~987
麻海春,王艳芬,冯春生,曾维安,孙丽华,卢宝顺,赵华. 2005.大鼠脑干网状结构胆碱能神经兴奋在疼痛信号传导中的作用.中华医学杂志, 85(12): 852~853
马金霞,张建富,李嘉陵,李兰亚,杨莉,费海霞. 2001.平均红细胞体积,红细胞体积分布宽度临床意义的分析.南京医科大学学报(自然科学版), 21(2): 135~136
马尧,路浩,赵宝玉,来航线,李蓉,王占新,陈基萍,卢围,荣杰. 2010.产苦马豆素真菌的筛选与鉴定.畜牧兽医学报, 41(5): 621~629
聂礼飞,巴杭阿吉艾克拜尔艾萨. 2009.苦马豆素全合成新进展.有机化学, 29(09): 1354~1361
荣杰,路浩,赵宝玉,王占新,卢围,马尧,李蓉. 2010.美国有毒植物概述及其对畜牧业生产的影响.中国农业科学, 43(17): 3633~3644
沈明华,莫重辉,赵宝玉,王占新. 2010.家兔实验性甘肃棘豆中毒的临床症状,病理形态学观察.动物医学进展, 31(1): 44~49
沈明华,莫重辉,赵宝玉. 2011.甘肃棘豆对家兔血液生化指标的影响.动物医学进展, 32(2): 52~55
史志诚等. 1997.中国草地重要有毒植物.北京:中国农业出版社
舒劲,李喜香,任远,李生财,吴国泰,洪秋菊. 2011.制萎扶胃浓缩丸对慢性萎缩性胃炎模型大鼠SOD活性、MDA和NO含量的影响.中国实验方剂学杂志, 17(2): 160~162
宋毓民. 2009. SW-BSA人工合成抗原疫苗的研究. [博士学位论文].陕西杨凌:西北农林科技大学苏进才. 1990.家畜小花棘豆中毒病的诊断和防治.中国兽医科技, (03): 29-30
孙以方,白德成,张文慧. 1998.医学实验动物学教程.郑州:河南医科大学出版社
童德文,曹光荣,赵献军. 2001.豆类丝核菌中生物碱的提取及苦马豆素含量测定.西北农业学报, (03): 1~3
童德文,董强,赵宝玉,付广建,张瑾. 2006.用甘肃棘豆草粉饲喂苦马豆素-BSA免疫山羊的血清相关酶分析.中国兽医科学, 36(4): 331~335
王凯. 1990.黄花棘豆对山羊的毒性研究.畜牧兽医学报, 21(1): 80~86
王凯,杨枝,王存寿. 1995.绵羊实验性甘肃棘豆中毒的病理学研究.中国兽医学报, 15(4): 391~394
王凯,莫重辉,赵宝玉,曹光荣. 1999.“棘防E号”预防绵羊甘肃棘豆中毒.畜牧与兽医, 31(3):
王建华,张志恒,高巨星. 1998.西藏阿里地区动物“醉马草”中毒病调查报告.动物毒物学, 13(1-2): 22~27
王建军. 2007.茎直黄芪化学成分研究及其提取物体外抑菌活性试验. [硕士学位论文].陕西杨凌:西北农林科技大学
王俊东,刘宗平. 2004.兽医临床诊断学.北京:中国农业出版社
吴永魁,常国权. 2003.黄花棘豆生物碱对体外大鼠卵黄囊胎盘结构及功能的影响.西北农林科技大学学报(自然科学版), (01): 117~120.
杨雅莹,李艳青,易永芬,何婷婷,肖钟. 2010.高尔基体α-甘露糖苷酶Ⅱ在胃癌中的表达及其与E-cadherin、Galectin-3的关系.重庆医科大学学报, 35(9): 1313~1317
杨志钊,杨山虹,黄福达,缪丽韶,张秀明. 2010.红细胞分布宽度在小细胞低色素性贫血中的意义.检验医学, 25(4): 982~987
张琦,张大方. 2010.乌头类生物碱对慢性心衰大鼠心肌SOD活性和MDA含量的影响.时珍国医国药, 21(11): 2812~2813
张坤生,田荟琳. 2007.过氧化氢酶的功能及研究.食品科技, (1): 8~11
张生民,高其栋,侯德慧,李欧,陈家茂,朱效文. 1981.甘肃棘豆中毒.畜牧兽医学报12(3): 145~150
张志敏,王建华,赵兴华,余永涛,刘志滨,耿果霞,马保华,赵晓娥. 2008.苦马豆素对小鼠细胞免疫功能的影响.西北农林科技大学学报(自然科学版), 36(2): 61~66
赵宝玉,曹光荣,童德文,王凯,莫重辉. 1999.“棘防C”预防山羊甘肃棘豆中毒初探.动物医学进展, 21(1): 42~44
赵宝玉. 2001.疯草(甘肃棘豆)生物碱系统分析及其毒性的比较病理学研究. [博士学位论文].陕西杨凌:西北农林科技大学
赵宝玉,刘忠艳,万学攀,霍星华,郭玺,王建军,孙莉莎,史志诚. 2008.中国西部草地毒草危害及治理对策.中国农业科学, 41(10): 3094~3103
赵宝玉,王保海,莫重辉,董强,格罗,四朗玉珍,秀华,土登,索多. 2009.西藏阿里地区牲畜醉马草中毒灾害调查及其综合利用.中国畜牧兽医学会2009学术年会, 353~359
周玫,陈瑗. 1992.自由基医学.北京:人民军医出版社
周维善. 1993.苦马豆素的不对称合成研究.第五届全国天然有机化学学术会议,广州:化学工业出版社
朱甘培,周维书,周维经. 1984.甘肃棘豆的初步研究.中国草地学报, (4): 469~471
Armien A G, Tokarnia C H, Peixoto P V, Barbosa J D, Frese K. 2011. Clinical and morphologic changes in ewes and fetuses poisoned by Ipomoea Carnea subspecies fistulosa. Journal of Veterinary Diagnostic Investigation, 23(2): 221~232
Benett R B, Choi J R, Montgomery W D, Cha J K. 1989. A short enantioselective synthesis of (-)-swainsonine. Journal of the American Chemical Society, 111: 2580~2582
Bernon C, Carre Y, Kuokkanen E, Slomianny M C, Mir A M, Krzewinski F, Cacan R, Heikinheimo P, Morelle W, Michalski J C, Foulquier F, Duvet S. 2011. Overexpression of Man2C1 leads to protein underglycosylation and upregulation of endoplasmic reticulum-associated degradation pathway. Glycobiology, 21(3): 363~375
Bianchi P, Fermo E, Vercellati C, Boschetti C, Barcellini W, Iurlo A, Marcello A P, Righetti P G, Zanella A. 2009. Congenital dyserythropoietic anemia type II (CDAII) is caused by mutations in the SEC23B gene. Hum Mutat, 30(9): 1292~1298
Bowlin T L, Sunkara P S. 1988. Swainsonine, an inhibitor of glycoprocessing, enhances mitogen induced interleukin-2 production and receptor expression in human lymphocytes. Biochemical and Biophysical Research Communications, 151(2): 859~864
Braun K, Romero J, Liddell C, Creamer R. 2003. Production of swainsonine by fungal endophytes of locoweed. Mycological Research, 107: 980~988
Broquist H P, Mason P S, Wickwire B, Homann R, Schneider M J, Harris T M. 1984. Swainsonine production in the mold Rhizoctonia legumenicola. Plant Toxicology, 5(14-18): 301~307
Bruni I, De Mattia F, Galimberti A, Galasso G, Banfi E, Casiraghi M, Labra, M. 2010. Identification of poisonous plants by DNA barcoding approach. Int J Legal Med, 124(6): 595~603
Cobucci-Ponzano B, Conte F, Strazzulli A, Capasso C, Fiume I, Pocsfalvi G, Rossi M, Moracci M. 2010.
The molecular characterization of a novel GH38 alpha-mannosidase from the crenarchaeon Sulfolobus solfataricus revealed its ability in de-mannosylating glycoproteins. Biochimie, 92(12): 1895~1907
Colegate S M, Dorling P R, Huxtable C R. 1979. A spectroscopic inestigation of swainsonine: an α-mannosidase inhibitor isolated from Swainsona Canescens. Aust J Chem, 32: 2257~2264
Colodel E M, Gardner D R, Zlotowski P, Driemeier D. 2002. Identification of swainsonine as a glycoside inhibitor responsible for Sida carpinifolia poisoning. Veterinary And Human Toxicology, 44(3): 177~178
Cook D, Ralphs M, Welch K, Stegelmeier B. 2009. Locoweed Poisoning in Cattle. Rangelands, 31(1): 16~21
Cook D, Gardner D R, Grum D, Pfister J A, Ralphs M H, Welch K D Green B T. 2011. Swainsonine and Endophyte Relationships in Astragalus mollissimus and Astragalus lentiginosus. Journal of Agricultural and Food Chemistry, 59(4): 1281~1287
Couch J F. 1929. A Contribution to The Study of Locoism. J Pharmacol Exp Ther, 36:55-83
Damme M, Morelle W, Schmidt B, Andersson C, Fogh J, Michalski J C, Lubke T. 2010. Impaired lysosomal trimming of N-linked oligosaccharides leads to hyperglycosylation of native lysosomal proteins in mice with alpha-mannosidosis. Molecular And Cellular Biology, 30(1): 273~283
Daniel P F, Winchester B, Warren C D. 1994. Mammalian alpha-mannosidases--multiple forms but a common purpose?. Glycobiology, 4(5): 551~566
Davis T Z, Lee S T, Ralphs M H, Panter K E. 2009. Selected common poisonous plants of the United States’Rangelands. Rangelands, 31(1): 38~44
Dennis J W, Koch K, Yousefi S, VanderElst I. 1990. Growth inhibition of human melanoma tumor xenografts in athymic nude mice by swainsonine. Cancer Res, 50(6): 1867~1872
DeSantis R, Santer U V, Glick M C. 1987. NIH 3T3 cells transfected with human tumor DNA lose the transformed phenotype when treated with swainsonine. Biochemical and Biophysical ResearchCommunications, 142(2): 348~353
Dohi K, Isoyama-Tanaka J, Misaki R, Fujiyama K. 2011. Jack bean alpha-mannosidase digestion profile of hybrid-type N-glycans: Effect of reaction pH on substrate preference. Biochimie, 93(4): 766~771
Driemeier D, Colodel E M, Gimeno E J, Barros S S. 2000. Lysosomal storage disease caused by Sida carpinifolia poisoning in goats. Veterinary Pathology, 37(2): 153~159
Galustian C, Foulds S, Dye J F, Guillou P J. 1994. Swainsonine, a glycosylation inhibitor, enhances both lymphocyte efficacy and tumour susceptibility in LAK and NK cytotoxicity. Immunopharmacology, 27(2): 165~172
Gardner D R, Cook D. 2011. A Comparison of Alternative Sample Preparation Procedures for the Analysis of Swainsonine using LC-MS/MS. Phytochemical. Analysis, 22(2): 124~127
Goss P E, Baptiste J, Fernandes B, Baker M, Dennis J W. 1994. A phase-I study of swainsonine in patients with advanced malignancies. Cancer Research, 54(6): 1450~1457
Goss P E, Reid C L, Bailey D, Dennis J W. 1997. Phase IB clinical trial of the oligosaccharide processing inhibitor swainsonine in patients with advanced malignancies. Clinical Cancer Research, 3(7): 1077~1086
Gregg K J, Zandberg W F, Hehemann J H, Whitworth G E, Deng L, Vocadlo D J, Boraston A B. 2011.
Analysis of a new family of widely distributed metal-independent {alpha}-mannosidases provides unique insight into the processing of N-linked glycans. J Biol Chem, 286(17): 15586~15596
Gupta R C. 2007. Veterinary toxicology: basic and clinical principles. Oxford. Academic Press: 825~872
Haraguchi M, Gorniak S L, Ikeda K, Minami Y, Kato A, Watson A A, Nash R J, Molyneux R J, Asano N. 2003. Alkaloidal components in the poisonous plant, Ipomoea carnea (Convolvulaceae). Journal of Agricultural And Food Chemistry, 51(17): 4995~5000
Hembre E J, Pearson W H. 1997. Synthesis of the novel mannosidase inhibitors (3R)- and (3S)-3-(hydroxymethyl)swainsonine. Tetrahedron, 53(32): 11021~11032
Hino M, Nakayama O, Tsurum Y, Adachi K, Shibata T, Terano H, Kohsaka M, Aoki H, Imanaka H. 1985.
Studies of an immunomodulator swainsonine I Enhance-ment of immune response by swainsonine in vitro. Journal of Antibiotics, 38: 926~935
Hosokawa N, Tremblay L O, Sleno B, Kamiya Y, Wada I, Nagata K, Kato K, Herscovics A. 2010. EDEM1 accelerates the trimming of alpha 1,2-linked mannose on the C branch of N-glycans. Glycobiology, 20(5): 567~575
Hossain M A, Nakano R, Nakamura K, Hossain M T, Kimura Y. 2010. Molecular characterization of plant acidic alpha-mannosidase, a member of glycosylhydrolase family 38, involved in the turnover of N-glycans during tomato fruit ripening. Journal of Biochemistry, 148(5): 603~616
Intra J, De Caro D, Perotti M E, Pasini M E. 2011. Glycosidases in the plasma membrane of Ceratitis capitata spermatozoa. Insect Biochemistry And Molecular Biology, 41(2): 90~100
James L F, Shupe J L, Binns W, Keeler R F. 1967. Abortive and teratogenic effects of locoweed on sheep and cattle. Am J Vet Res, 28(126): 1379~1388
James L F, Elein A D, Molyneux R J, Warren C D. 1989. Toxic species of the plant genus swainsona. In swainsonine and related Glycosidase Inhibitors. Ames, Iowa : Iowa State Univesity press: 14~22
James L F, Panter K E, Broquist H P, Hartley W J. 1991. Swainsonine induced high mountain disease in calves. Vet Hum Toxi-col, 33(3): 217~219
Karasuno T, Kanayama Y, Nishiura T, Nakao H, Yonezawa T, Tarui S. 1992. Glycosidase inhibitors (castanospermine and swainsonine) and neuraminidase inhibit pokeweed mitogen-induced B cell maturation. Eur J Immunol, 22(8): 2003~2008
Kino T, Inamura N, Nakahara K, Kiyoto S, Goto T, Terano H, Kohsaka M, Aoki H, Imanaka, H 1985. Studies of an immunomodulator, swainsonine. II. effect of swainsonine on mouse immunodeficient system and experimental murine tumor. J Antibiot (Tokyo), 38(7): 936~40
Kukuruzinska M A, Lennon K. 1998. Protein N-glycosylation: molecular genetics and functional significance. Crit Rev Oral Biol Med, 9(4): 415~418
Liebmingera E, Hüttnera S, Vavraa U, Fischla R, Schoberera J, Grassb J, Blaukopfc C, Seifertc G J, Altmannb F L, M, Strassera R. 2009. Class Iα-mannosidases are required for N-glycan processing and root development in arabidopsis thaliana. The Plant Cell, 21: 3850~3867
Malm D, Nilssen O. 2008. Alpha-mannosidosis. Orphanet Journal of Rare Diseases, 3(1): doi:10.1186/1750-1172-3-21
Matsuda K, Kurakata Y, Miyazaki T, Matsuo I, Ito Y, Nishikawa A, Tonozuka T. 2011. Heterologous expression, purification, and characterization of an alpha-mannosidase belonging to glycoside hydrolase family 99 of shewanella amazonensis. Biosci Biotechnol Biochem, 75(4): 797~9
Molyneux R J, James L F. 1982. Loco intoxication indolizidine alkaloids of spotted loeoweed (astragalus lentiginosus). Seienee, 216: 190~191
Mora-Montes H M, Robledo-Ortiz C I, Gonzalez-Sanchez L C, Lopez-Esparza A, Lopez-Romero E, Flores-Carreon A. 2010. Purification and biochemical characterisation of endoplasmic reticulum alpha 1,2-mannosidase from Sporothrix schenckii. Memorias Do Instituto Oswaldo Cruz, 105(1): 79~85
Moremen K W. 2002. Golgi alpha-mannosidase II deficiency in vertebrate systems: implications for asparagine-linked oligosaccharide processing in mammals. Biochim Biophys Acta, 1573(3): 225~35
Mukherjee S, Dawe A L, Creamer R. 2010. Development of a transformation system in the swainsonine producing, slow growing endophytic fungus, Undifilum oxytropis. J Microbiol Methods, 81(2): 160~5
Panter K E, James L F, Stegelmeier B L, Ralphs M H, Pfister J A. 1999. Locoweeds: Effects on reproduction in livestock. Journal of Natural Toxins, 8(1): 53~62
Panter K E, Wierenga T L, Pfister J A. 2007. Poisonous plants: global research and solutions. cabdirect Press: 359~365
Pedroso P, de Oliveira L, Cruz C, Soares M P, Barreto L, Driemeier D. 2010. Lysosomal storage disease caused by Sida carpinifolia in cattle in Rio Grande do Sul. Pesquisa Veterinaria Brasileira, 30(10): 833~838
Pemberton R W,Turner C E. 1990. Biological control of senecio jacobaea in Northern California, an enduring success. Entomophag, 35(1): 71~77
Pfister, J A, Stegelmeie, B L, Cheney, C D. 2002. Conditioning taste aversions to locoweed (Oxytropis sericea) in horses. Journal of Animal Science, (1): 79~83
Pomerinke M A, Thompson D C, Clason D L. 1995. Bionomics of cleonidius trivittatus (Coleoptera: Curculionidae): native biological Control of purple locoweed (Rosales: Fabaceae). Environmental Entomology, 26(6): 1696~1702
Pyne S G. 2005. Recent Developments on the Synthesis of (-)-Swainsonine and Analogues. Current Organic Synthesis, 2(1): 39~57
Ralphs M H, Monaco T A. 2007. Seeding cool-season grasses to suppress white locoweed (oxytropis sericea) reestablishment and increase forage production. Weed Technology, 21(3): 661
Romero J M, Creamer R, Zepeda H, Strickland J, Bell G. 2004. The toxicosis of Embellisia fungi from locoweed (Oxytropis lambertii) is similar to locoweed toxicosis in rats. Journal of Animal Science, 82(7): 2169~2174
Schneider M J, Ungemach F S, Broquist H P, Harris T M. 1983. (1S, 2R, 8R, 8aR)-1, 2, 8-trihydroxyoctahydroindolizine (swainsonine), anα-mannosidase inhibitor from Rhizoctonia leguminicola. Tetrahedron, 39(29~32)
Schroder S, Matthes F, Hyden P, Andersson C, Fogh J, Muller-Loennies S, Braulke T, Gieselmann V, Matzner U. 2010. Site-specific analysis of N-linked oligosaccharides of recombinant lysosomal arylsulfatase A produced in different cell lines. Glycobiology, 20(2): 248~259
Shaheen P E, Stadler W, Elson P, Knox J, Winquist E, Bukowski R M. 2005. Phase II study of the efficacy and safety of oral GD0039 in patients with locally advanced or metastatic renal cell carcinoma. Investigational New Drugs, 23(6): 577~581
Shashidhara K S, Gaikwad S M. 2009. Class II alpha-mannosidase from Aspergillus fischeri: Energetics of catalysis and inhibition. International Journal of Biological Macromolecules, 44(1): 112~115
Shashidhara, K S, Gaikwad S M. 2010. Conformational and Functional Transitions in Class II alpha-mannosidase from Aspergillus fischeri. Journal of Fluorescence, 20(4): 827~836
Stegelmeier B L, Molyneux R J, Elbein A D, James L F. 1995. The lesions of locoweed (Astragalus mollissimus), swainsonine, and castanospermine in rats. Vet Pathol, 32(3): 289~98
Stegelmeier B L, Ralphs M H, Gardner D R, Molyneux R J, James L F. 1994. Serum alpha-mannosidase activity and the clinicopathologic alterations of locoweed (Astragalus mollissimus) intoxication in range cattle. J Vet Diagn Invest, 6(4): 473~479
Sun J Y, Yang H, Miao S, Li J P, Wang S W, Zhu M Z, Xie Y H, Wang J B, Liu Z, Yang Q. 2009.
Suppressive effects of swainsonine on C6 glioma cell in vitro and in vivo. Phytomedicine, 16(11): 1070~1074
Tamerler C, Ullah M, Adlard M W, Keshavarz T. 1998. Effect of pH on physiology of Metarhizium anisopliae for production of swainsonine. Fems Microbiology Letters. 168(1): 17~23
Tong D, Mu P, Dong Q, Zhao B, Liu W, Zhao J, Li L, Zhou T, Wang J, Sui G. 2007.Immunological evaluation of SW-HSA conjugate on goats. Colloids Surf B Biointerfaces, 58(1): 61~67
Tulsiani D R, P B H, James L F, Touster O. 1984. The similar effects of swainsonine and locoweed on tissue glycosidases and oligosaccharides of the pig indicate that the alkaloid is the principle toxin responsible for the induction of locoism. Arch Biochem Biophys, 232(1): 76~85 Uno Y, Hashidume S, Kurita O, Fujiwara T, Nomura K. 2010. Dioscorea opposita
Thunb.alpha-mannosidase belongs to the glycosyl hydrolase family 38. Acta Physiologiae Plantarum, 32(4): 713~718
USDA/ARS. 2011. Cool-season grasses to suppress broom snakeweed, downy brome and weedy forbs. http://www.ars.usda.gov/research/publications/publications.htm?SEQ_NO_115=233791[2010-03-05]
Wang Y, Hu Y C, Wang J H, Yu Y T, Song Y M, Yang G D, Geng G X. 2010. Isolation and characterization of Arthrobacter sp HW08 capable of biodegrading swainsonine. African Journal of Microbiology Research, 4(15): 1635~1638
Wikipedia. 2011. List of glycoside hydrolase families. http://en.wikipedia.org/wiki/List_of_glycoside_hydrolase_families[2011-04-10]
Yasuda N, Tsutsumi H, Takaya T. 1984. Total synthesis of swainsonine. Chemistry Letters, 13(7): 1201~1204
Yu Y T, Zhao Q M, Wang J N, Wang J H, Wang Y, Song Y M, Geng G X, Li Q F. 2010.
Swainsonine-producing fungal endophytes from major locoweed species in China. Toxicon, 56(3): 330~338
Zeng Y C, Pan Y T, Asano N, Nash R J, Elbein A D. 1997. Homonojirimycin and N-methyl-homonojirimycin inhibit N-linked oligosaccharide processing. Glycobiology, 7(2): 297~304
Zhou J, Lin C Z, Zheng X Z, Lin X J, Sang W J, Wang S H, Wang Z H, Ebbole D, Lu G D. 2009.
Functional analysis of an alpha-1, 2-mannosidase from magnaporthe oryzae. Current Genetics, 55(4): 485~496
Zhu Y P, Suits M D L, Thompson A J, Chavan S, Dinev Z, Dumon C, Smith N, Moremen K W, Yong X, Siriwardena A, Williams S J, Gilbert H J, Davies G J. 2010. Mechanistic insights into a Ca2+-dependent family ofα-mannosidases in a human gut symbiont. Nature Chemical Biology, 6(2): 125~132