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     (±)-Blebbistatin 是一種細(xì)胞滲透性非肌肉肌球蛋白II ATP酶抑制劑，其IC50范圍為2微米[1，2]。 非肌肉肌球蛋白II (NM II)，一種肌動(dòng)蛋白結(jié)合蛋白，在細(xì)胞遷移、粘附和分化的調(diào)節(jié)中起著重要作用[4]。最近對NM II在這些過程中的重要性的深入了解通過基因缺失和突變方法得到了強(qiáng)調(diào)，這些方法發(fā)現(xiàn)NM II突變會(huì)影響多種蛋白質(zhì)的功能并導(dǎo)致單基因疾病[5.6]。

   (±)-Blebbistatin 是一種小分子抑制劑，優(yōu)先與肌球蛋白-ADP-Pi復(fù)合物結(jié)合，以減緩磷酸鹽釋放[2]。該抑制劑在體外完全消除了肌動(dòng)蛋白激活Mg-ATPase活性的收縮和肌球蛋白II的運(yùn)動(dòng)性(IC50 = 0.5-5.0微米)[8，9]，但其對平滑肌肌球蛋白II (IC50 =80微米)和肌球蛋白I、V和X的作用較差[3]。此外，blebbistatin可有效抑制哺乳動(dòng)物動(dòng)脈平滑肌(IC50=5微米)[9]。blebbistatin阻斷肌動(dòng)蛋白分離狀態(tài)的肌球蛋白II并防止剛性肌動(dòng)球蛋白交聯(lián)的特性在體內(nèi)應(yīng)用中是一個(gè)巨大的優(yōu)勢[2，11]。

     在恒壓格蘭特灌注模型系統(tǒng)中，用blebbistatin (10-200 M)處理CB和TM細(xì)胞，細(xì)胞形態(tài)改變，肌動(dòng)蛋白應(yīng)力纖維含量降低。blebbistatin效應(yīng)在24小時(shí)內(nèi)完全可逆[10]。Blebbistatin抑制單細(xì)胞收縮，而不改變細(xì)胞內(nèi)鈣瞬變的形態(tài)(IC50 = 0.43微米)。暴露于波長低于488 nm的紫外光下也可導(dǎo)致blebbistatin迅速被抑制。[8].

產(chǎn)品性質(zhì)：

Cas No.:674289-55-5

化學(xué)名:3a-hydroxy-6-methyl-1-phenyl-3,3a-dihydro-1H-pyrrolo[2,3-b]quinolin-4(2H)-one

Canonical SMILES:OC12CCN(C1=NC3=C(C2=O)C=C(C=C3)C)C4=CC=CC=C4

分子式:C18H16N2O2

分子量:292.34

溶解度:10mg/mL in DMSO, 20mg/mL in DMF

儲(chǔ)存條件:Store at -20°C,unstable in solution, ready to use.

注意事項(xiàng)：

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References:

[1].  Straight AF, Cheung A, Limouze J, et al. Dissecting temporal and spatial control of cytokinesis with a myosin II Inhibitor. Science, 2003, 299:1743–1747.

[2].  Kovacs M, Toth J, Hetenyi C, Malnasi-Csizmadia A, Sellers JR. Mechanism of blebbistatin inhibition of myosin II. J Biol Chem, 2004, 279:35557–35563.

[3].  Limouze J, Straight AF, Mitchison T, Sellers JR. Specificity of blebbistatin, an inhibitor of myosin II. J Muscle Res Cell Motil, 2004, 25:337–341.

[4].  Miguel Vicente-Manzanares, Xuefei Ma, Robert S. Adelstein,Alan Rick Horwitz. Non-muscle myosin II takes centre stage in cell adhesion and migration.Nat Rev Mol Cell Biol, 2009 Nov, 10(11): 778–790.

[5].  Burt RA, Joseph JE, Milliken S, Collinge JE, Kile BT. Description of a novel mutation leading to MYH9-related disease. Thrombosis Research, 2008, 122(6): 861-863.

[6].  Butcher DT, Alliston T, Weaver VM. A tense situation: forcing tumour progression. Nature Reviews Cancer, 2009 Feb, 9(2):108-122.

[7].  Chen Y, Boukour S, Milloud R, Favier R, Saposnik B, Schlegel N, et al. The abnormal proplatelet formation in MYH9-related macrothrombocytopenia results from an increased actomyosin contractility and is rescued by myosin IIA inhibition. Journal of thrombosis and haemostasis : JTH , 2013, 11:2163-2175.

[8].  Fedorov VV, Lozinsky IT, Sosunov EA, Anyukhovsky EP, Rosen MR, Balke CW, et al. Application of blebbistatin as an excitation-contraction uncoupler for electrophysiologic study of rat and rabbit hearts. Heart rhythm: the official journal of the Heart Rhythm Society, 2007, 4:619-626.

[9].  Zhang X-h, Aydin M, Kuppam D, Melman A, DiSanto ME. In Vitro and In Vivo Relaxation of Corpus Cavernosum Smooth Muscle by the Selective Myosin II Inhibitor, Blebbistatin. The Journal of Sexual Medicine, 2009, 6:2661-2671.

[10].  Zhang M, Rao PV. Blebbistatin, a novel inhibitor of myosin II ATPase activity, increases aqueous humor outflow facility in perfused enucleated porcine eyes. Investigative ophthalmology & visual science, 2005, 46:4130-4138.

[11].  Lucas-Lopez C, Allingham JS, Lebl T, Lawson CP, Brenk R, Sellers JR, et al. The small molecule tool (S)-(-)-blebbistatin: novel insights of relevance to myosin inhibitor design. Organic & biomolecular chemistry, 2008, 6:2076-2084.