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Cortistatin 14

(Synonyms: CST-14, human, rat) 目录号 : GC12835 复制 一键复制产品信息

Cortistatin 14是一种神经肽,主要存在于大脑皮层和海马体中,可抑制海马CA1神经元的放电活动。

Cortistatin 14 Chemical Structure

Cas No.:193829-96-8

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Description

Cortistatin 14, a neuropeptide, is present primarily in the cortex and hippocampus, which inhibits neuronal firing of hippocampal CA1 neurons [1]. Cortistatin 14 inhibits the proliferation of Th1 cells and release of pro-inflammatory cytokines (IL-2 and IFN-γ), while increasing anti-inflammatory signals (IL-10) [2]. Cortistatin 14 has been widely used to regulate the central nervous function of mice and to modulate the sleep/wake rhythm[3].

In vitro, Cortistatin 14 (1µM) treatment for 48 hours significantly inhibited the proliferation of WRO cells[4].

In vivo, Cortistatin 14 treatment via a single intraperitoneal injection at a dose of 500µg/kg significantly increased the survival rate of septic mice within one week and improved cognitive and emotional dysfunction[5]. Ten minutes before intraperitoneal injection of 10mg/kg kainate, 5µl of 10nmol Cortistatin 14 was intracerebroventricularly injected, which significantly reduced the epileptic seizures in rats and inhibited the significant reduction of cortical and hippocampal neurons in rats[6]. A single intraperitoneal injection of 1mg/kg dose of Cortistatin 14 significantly inhibited gastrointestinal transit, microsphere excretion, and fecal particle excretion in mice with colitis[7]. Intracerebroventricular injection of a single dose of 5µg Cortistatin 14 can alleviate depressive-like behaviors in mice and reduce the time spent in inactivity by the mice within 10 minutes[8].

References:
[1] Flood J F, Uezu K, Morley J E. The cortical neuropeptide, cortistatin-14, impairs post-training memory processing[J]. Brain research, 1997, 775(1-2): 250-252.
[2] Markovics A, Szőke É, Sándor K, et al. Comparison of the anti-inflammatory and anti-nociceptive effects of cortistatin-14 and somatostatin-14 in distinct in vitro and in vivo model systems[J]. Journal of Molecular Neuroscience, 2012, 46(1): 40-50.
[3] de Lecea L. Cortistatin—functions in the central nervous system[J]. Molecular and cellular endocrinology, 2008, 286(1-2): 88-95.
[4] Cassoni P, Muccioli G, Marrocco T, et al. Cortistatin-14 inhibits cell proliferation of human thyroid carcinoma cell lines of both follicular and parafollicular origin[J]. Journal of endocrinological investigation, 2002, 25(4): 362-368.
[5] Wen Q, Ding Q, Wang J, et al. Cortistatin‐14 Exerts Neuroprotective Effect Against Microglial Activation, Blood‐brain Barrier Disruption, and Cognitive Impairment in Sepsis‐associated Encephalopathy[J]. Journal of immunology research, 2022, 2022(1): 3334145.
[6] Braun H, Schulz S, Becker A, et al. Protective effects of cortistatin (CST-14) against kainate-induced neurotoxicity in rat brain[J]. Brain research, 1998, 803(1-2): 54-60.
[7] Jiang J H, Jin W D, Peng Y L, et al. The role of Cortistatin-14 in the gastrointestinal motility in mice[J]. Pharmacological Reports, 2018, 70(2): 355-363.
[8] Jiang J H, Peng Y L, Liang X Y, et al. Centrally administered cortistation-14 induces antidepressant-like effects in mice via mediating ghrelin and GABAA receptor signaling pathway[J]. Frontiers in Pharmacology, 2018, 9: 767.

Cortistatin 14是一种神经肽,主要存在于大脑皮层和海马体中,可抑制海马CA1神经元的放电活动[1]。Cortistatin 14可抑制Th1细胞增殖及促炎细胞因子(IL-2和IFN-γ)的释放,同时增加抗炎信号(IL-10)[2]。Cortistatin 14已被广泛用于调节小鼠中枢神经功能及睡眠/觉醒节律[3]

在体外,1µM的Cortistatin 14处理48小时可显著抑制WRO细胞的增殖[4]

在体内,单次腹腔注射500µg/kg的Cortistatin 14可显著提高脓毒症小鼠一周内的存活率,并改善认知和情绪功能障碍[5]。在腹腔注射10mg/kg红藻氨酸前10分钟,脑室内注射5µl 10nmol的Cortistatin 14,可显著减少大鼠癫痫发作,并抑制大鼠皮层和海马神经元的显著减少[6]。单次腹腔注射1mg/kg的Cortistatin 14可显著抑制结肠炎小鼠的胃肠蠕动、微球排泄及粪便颗粒排泄[7]。脑室内注射单剂量5µg的Cortistatin 14可在10分钟内减轻小鼠抑郁样行为,并减少小鼠的不动时间[8]

实验参考方法

Cell experiment [1]:

Cell lines

WRO cells

Preparation Method

WRO cells were grown as a monolayer in RPMI medium with 10% fetal calf serum at 37℃ in a 5% CO2 humidified atmosphere. cells were seeded in quadruplicate in 48-multiwell plates (10000 cells/well) in standard culture medium and allowed to attach for 24h. Cortistatin 14 (0.001, 0.01, 0.1, and 1µM) were then added to the medium and cells were treated up to 96h. Cell viability was evaluated.

Reaction Conditions

0.001, 0.01, 0.1, and 1µM; 96h

Applications

Cortistatin 14 treatment significantly reduced the cell viability of WRO cells in a dose-dependent manner.
Animal experiment [2]:

Animal models

Kunming Mice

Preparation Method

Male Kunming mice (weighing 20-24g) were housed in sawdust-lined plastic cages and were maintained at 22±1°C (12h light/dark cycle). Drinking water and food were available ad libitum. Establish a mouse model of colitis using dextran sulfate sodium. Mice were fasted for 24h, intraperitoneal injection of Cortistatin 14 (1mg/kg) after five minutes, and were gavaged with 200µl charcoal marker (10%, charcoal suspension in 5% gum arabic solution). The mice were killed 30 minutes after intragastric (i.g.) administration, and the small intestine was removed. The distance traveled by the charcoal marker was measured.

Dosage form

1mg/kg for once; i.p.

Applications

Cortistatin 14 treatment significantly inhibited gastrointestinal transit in mice with colitis.

References:
[1] Cassoni P, Muccioli G, Marrocco T, et al. Cortistatin-14 inhibits cell proliferation of human thyroid carcinoma cell lines of both follicular and parafollicular origin[J]. Journal of endocrinological investigation, 2002, 25(4): 362-368.
[2] Jiang J H, Jin W D, Peng Y L, et al. The role of Cortistatin-14 in the gastrointestinal motility in mice[J]. Pharmacological Reports, 2018, 70(2): 355-363.

化学性质

Cas No. 193829-96-8 SDF
别名 CST-14, human, rat
化学名 (S)-2-((Z)-(((4R,5Z,7S,8E,10S,11Z,13S,14Z,16S,17Z,19S,20Z,22S,23Z,25S,26Z,28S,29Z,31S,32Z,34S,35Z,37R)-22-((1H-indol-3-yl)methyl)-19,34-bis(4-aminobutyl)-13,25,28-tribenzyl-6,9,12,15,18,21,24,27,30,33,36-undecahydroxy-37-((Z)-(hydroxy((S)-pyrrolidin-2-yl)
Canonical SMILES C[C@](O)([H])[C@@]1([H])/C(O)=N/[C@@](/C(O)=N/[C@@](/C(O)=N\[C@@](/C(O)=N/[C@@](/C(O)=N/[C@@](C(O)=O)([H])CCCCN)([H])CSSC[C@@](/N=C(O)/[C@]2([H])CCCN2)([H])/C(O)=N/[C@@](/C(O)=N/[C@@](/C(O)=N/[C@@](/C(O)=N/[C@@](/C(O)=N/[C@@](/C(O)=N/[C@@](/C(O)=N/1)([H])
分子式 C81H113N19O19S2 分子量 1721.03
溶解度 1mg/mL in water 储存条件 Desiccate at -20°C
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1 mM 581 μL 2.9052 mL 5.8105 mL
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