牛磺熊去氧胆酸

牛磺熊去氧胆酸用途

Tauroursodeoxycholate 是一种内质网应激抑制剂。Tauroursodeoxycholate 显著降低凋亡分子如 caspase-3 和 caspase-12 表达。Tauroursodeoxycholate 也抑制 ERK。

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牛磺熊去氧胆酸名称

[ CAS 号 ]:
14605-22-2

[ 中文名 ]:
牛磺脱氧胆酸

[ 英文名 ]:
Tauroursodeoxycholic acid

[中文别名 ]:

[英文别名 ]:

Tauroursodeoxycholic acid sodium salt
MFCD00069496
Tauroursodeoxycholic acid dihydrate
Sodium tauroursodeoxycholate
TAUROURSODEOXYCHOLIC ACID

牛磺熊去氧胆酸生物活性

[ 描述 ]:

Tauroursodeoxycholate 是一种内质网应激抑制剂。Tauroursodeoxycholate 显著降低凋亡分子如 caspase-3 和 caspase-12 表达。Tauroursodeoxycholate 也抑制 ERK。

[ 相关类别 ]:

信号通路 >> 细胞凋亡 >> 胱天蛋白酶

天然产物 >> 酸和醛

研究领域 >> 癌症

[ 靶点 ]

ERK

Caspase-3

Caspase-12

Human Endogenous Metabolite

[体外研究]

牛磺熊去氧胆酸盐(TUDCA)通过PKCα诱导丝裂原活化蛋白激酶磷酸酶-1(MKP-1),通过抑制ERK磷酸化来抑制血管平滑肌细胞(VSMC)的活力和迁移。 Tauroursodeoxycholate通过抑制ERK,通过Ca2 +依赖性PKCα易位抑制VSMCs的增殖和迁移。牛磺熊去氧胆酸盐可预防血小板衍生生长因子(PDGF)和血管损伤诱导的MMP-9表达。使用特异性si-RNA敲低MKP-1可恢复Tauroursodeoxycholate(200μM)对VSMC生存力的降低,这表明牛磺熊去氧胆酸盐的抗增殖作用依赖于MKP-1的表达[1]。

[体内研究]

使用免疫组织化学检测牛磺熊去氧胆酸盐(TUDCA)对体内VSMC增殖和凋亡的影响,用于增殖细胞核抗原(PCNA)和转移酶dUTP缺口末端标记(TUNEL)测定。牛磺熊去氧胆酸盐(10,50和100mg/kg)以剂量依赖性方式增加受损组织的胱天蛋白酶3活性,表明牛磺熊去氧胆酸盐诱导新内膜中VSMC的凋亡。使用受损组织,与正常对照相比,在损伤后1周进行ERK和MMP-9表达的磷酸化水平的进一步检查和比较。球囊损伤增加了ERK的磷酸化和组织中MMP-9的表达。牛磺熊去氧胆酸盐(10,50和100 mg/kg)以剂量依赖的方式抑制ERK和MMP-9表达的磷酸化[1]。牛磺熊去氧胆酸盐(TUDCA)是亲水性胆汁酸。牛磺熊去氧胆酸盐作为细胞保护剂可改善肝功能,并可通过减少ER应激和细胞凋亡来预防肝细胞癌。 Tauroursodeoxycholate显着降低凋亡分子的表达,如caspase-3,caspase-12,C/EBP同源蛋白,c-Jun N末端激酶(JNK),激活转录因子4(ATF4),X-box结合蛋白(XBP) )和Ang II诱导的ApoE -/-小鼠中的真核起始因子2α(eIF2α)(p <0.05)。牛磺熊去氧胆酸盐降低ApoE -/-小鼠中血管紧张素(Ang)II诱导的腹主动脉瘤(AAA)形成。牛磺熊去氧胆酸盐以0.5g/kg /天的剂量用于治疗Ang II诱导的ApoE -/-小鼠(ER应激抑制剂组)。 AAA模型的收缩压(141.3±5.6 mmHg vs 145.9±8.9 mmHg; p> 0.05)和总胆固醇水平(663.6±88.7 mg/dL vs 655.7±65.4 mg/dL; p> 0.05)没有差异组和牛磺熊去氧胆酸盐组。此外,与AAA模型组相比,Tauroursodeoxycholate组的最大主动脉直径明显较小(0.95±0.03 mm vs 1.79±0.04 mm; p <0.05)。 Tauroursodeoxycholate组的AAA病变面积也小于AAA模型组(0.37±0.03 mm2 vs 1.51±0.06 mm2; p <0.05)[2]。

[细胞实验]

使用Ez-Cytox测量细胞活力和增殖。将VSMC（5×103细胞）接种到平滑肌细胞生长培养基2（SMCGM2）中的96孔板上并培养。血清饥饿后，将牛磺熊去氧胆酸盐（0,50,100和200μM）加入到hVSMC中，加入或不加1,2-双（邻氨基苯氧基）乙烷-N，N，N'，N'-四乙酸四（乙酰氧基甲基）酯（BAPTA，10μM）和7-羟基星形孢菌素（H7,10μM）并培养24小时。为了评估牛磺熊去氧胆酸盐对PDGF刺激的hVSMC增殖的影响，将hVSMC接种到96孔板上并培养。在血清饥饿后，将Tauroursodeoxycholate（0,50,100和200μM）加入到hVSMC中，有或没有PDGF-BB（50ng / mL）并培养。在每个孔中加入10μLEz-Cytox后，通过测量450nm处的光密度来评估细胞活力[1]。

[动物实验]

用组合麻醉剂（氯胺酮，70mg / kg;赛拉嗪，7mg / kg ip）麻醉大鼠[1] Sprague-Dawley大鼠。牛磺熊去氧胆酸盐每天口服给药一次，剂量不同（即载体，10,50和100mg / kg），持续2周。通过灌注4％甲醛固定颈动脉，然后将组织包埋在石蜡中，切片（8μm）用H＆E染色[1]。小鼠[2]将8周龄的ApoE - / - C57BL / 6雄性小鼠随机分为3组（每组n = 10）:( i）假手术并注射生理（0.9％）生理盐水作为载体（正常）：小组）; （ii）将小型渗透泵皮下植入ApoE - / - 小鼠的右侧，在28天的过程中释放Ang II（1000ng / kg / min）（AAA模型组）; （iii）在饮用水（牛磺熊去氧胆酸盐组）中以0.5g / kg /天的剂量每天用牛磺熊去氧胆酸盐处理4周的AAA模型小鼠。在Ang II输注28天后处死小鼠[2]。

[参考文献]

[1]. Kim SY, et al. Tauroursodeoxycholate (TUDCA) inhibits neointimal hyperplasia by suppression of ERK viaPKCα-mediated MKP-1 induction. Cardiovasc Res. 2011 Nov 1;92(2):307-16.

[2]. Qin Y, et al. Tauroursodeoxycholic Acid Attenuates Angiotensin II Induced Abdominal Aortic Aneurysm Formation in Apolipoprotein E-deficient Mice by Inhibiting Endoplasmic Reticulum Stress. Eur J Vasc Endovasc Surg. 2017 Mar;53(3):337-345.

[相关活性小分子]

牛磺熊去氧胆酸物理化学性质

[ 密度 ]:
1.2±0.1 g/cm3

[ 沸点 ]:
496.4ºC at 760mmHg

[ 熔点 ]:
173-175°C

[ 分子式 ]:
C₂₆H₄₅NO₆S

[ 分子量 ]:
499.70

[ 闪点 ]:
214.2ºC

[ PSA ]:
132.31000

[ LogP ]:
2.10

[ 外观性状 ]:
白色固体

[ 折射率 ]:
1.552

牛磺熊去氧胆酸MSDS

详细MSDS(安全技术说明书)

牛磺熊去氧胆酸毒性和生态

CHEMICAL IDENTIFICATION

RTECS NUMBER :: KI7372500

CHEMICAL NAME :: Ethanesulfonic acid, 2-(((3-alpha,5-beta,7-beta)-3,7-dihydroxy-24-oxochola n-24-yl)amino)-

CAS REGISTRY NUMBER :: 14605-22-2

LAST UPDATED :: 199309

DATA ITEMS CITED :: 4

MOLECULAR FORMULA :: C26-H45-N-O6-S

MOLECULAR WEIGHT :: 499.78

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: >5 gm/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: JKXXAF Japanese Kokai Tokyo Koho Patents. (U.S. Patent and Trademark Office, Foreign Patents, Washington, DC 20231) Volume(issue)/page/year: #92-235918

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 300 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: JKXXAF Japanese Kokai Tokyo Koho Patents. (U.S. Patent and Trademark Office, Foreign Patents, Washington, DC 20231) Volume(issue)/page/year: #92-235918

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: >6 gm/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: JKXXAF Japanese Kokai Tokyo Koho Patents. (U.S. Patent and Trademark Office, Foreign Patents, Washington, DC 20231) Volume(issue)/page/year: #92-235918

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 350 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: JKXXAF Japanese Kokai Tokyo Koho Patents. (U.S. Patent and Trademark Office, Foreign Patents, Washington, DC 20231) Volume(issue)/page/year: #92-235918

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牛磺熊去氧胆酸安全信息

[ 个人防护装备 ]:
Eyeshields;Gloves;type N95 (US);type P1 (EN143) respirator filter

[ 安全声明 (欧洲) ]:
S22-S24/25

[ 危险品运输编码 ]:
NONH for all modes of transport

[ WGK德国 ]:
2

[ RTECS号 ]:
KI7372500

牛磺熊去氧胆酸文献

Lysosomes and unfolded protein response, determinants of differential resistance of melanoma cells to vinca alkaloids.

Fundam. Clin. Pharmacol. 29(2) , 164-77, (2015)

On account of its strong ability to become chemoresistant after a primary response to drugs, malignant melanoma (MM) remains a therapeutic challenge. This study focuses on acquired resistance to vinca...

Regulation of host weight gain and lipid metabolism by bacterial bile acid modification in the gut.

Proc. Natl. Acad. Sci. U. S. A. 111(20) , 7421-6, (2014)

Alterations in the gastrointestinal microbiota have been implicated in obesity in mice and humans, but the key microbial functions influencing host energy metabolism and adiposity remain to be determi...

Tauroursodeoxycholic acid inhibits experimental colitis by preventing early intestinal epithelial cell death.

Lab. Invest. 94(12) , 1419-30, (2014)

Ulcerative colitis (UC) is characterized by increased epithelial cell death and subsequent breakdown of the intestinal epithelial barrier, which perpetuates chronic intestinal inflammation. Since feca...

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