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MOTS-c

目录号 : GC25648

MOTS-c是一种线粒体衍生的具有代谢调节功能的多肽。

MOTS-c Chemical Structure

Cas No.:1627580-64-6

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Sample solution is provided at 25 µL, 10mM.

Description

MOTS-c is a mitochondrial-derived polypeptide with metabolic regulatory functions [1]. MOTS-c exerts anti-injury and anti-inflammatory effects by activating the AMPK pathway and inhibiting the MAP kinase-c-fos signaling pathway [2]. MOTS-c can be used in studies on stress, inflammation, metabolism, neuroprotection, and aging [3].

In vitro, MOTS-c (0-100μM; 8-24 hours) can promote the phosphorylation of AMPK (Thr 172) and Akt (Ser 473) in HEK 293 cells in a time- and dose-dependent manner [4]. Different concentrations of MOTS-c (0, 2.5, 5, 10, 20 and 40μM; 24 hours) would weaken the inhibitory effect of hypoxia treatment on the inhibition of DR4, DR5, FADD and caspase-8 in HCC cells. MOTS-c weakens the resistance of liver cancer cells to TRAIL-induced apoptosis by activating MEF2A [5].

In vivo, male C57 BL/6 mice treated with MOTS-c (5mg/kg/day; i.p.) for 7 days significantly enhanced insulin-stimulated glucose clearance rate and improved insulin sensitivity in skeletal muscle [4]. Treating mice with MOTS-c (50mg/kg; i.p.) 4 hours before formalin treatment significantly reduced the levels of pro-inflammatory cytokines in mouse serum and increased the levels of anti-inflammatory cytokines. Additionally, MOTS-c treatment significantly increased the phosphorylation level of AMPKα, inhibited the activation of spinal extracellular signal-regulated kinase (ERK), c-Jun amino-terminal kinase (JNK), and P38 in mice induced by formalin, as well as the expression of c-fos [6].

References:
[1] Benayoun B A, Lee C. MOTS‐c: a mitochondrial‐encoded regulator of the nucleus[J]. Bioessays, 2019, 41(9): 1900046.
[2] Yin X, Jing Y, Chen Q, Abbas AB, Hu J, Xu H. The intraperitoneal administration of MOTS-c produces antinociceptive and anti-inflammatory effects through the activation of AMPK pathway in the mouse formalin test. Eur J Pharmacol. 2020 Mar 5;870:172909. 
[3] Wan W, Zhang L, Lin Y, et al. Mitochondria-derived peptide MOTS-c: effects and mechanisms related to stress, metabolism and aging[J]. Journal of Translational Medicine, 2023, 21(1): 36.
[4] Lee C, Zeng J, Drew BG, Sallam T, Martin-Montalvo A, Wan J, Kim SJ, Mehta H, Hevener AL, de Cabo R, Cohen P. The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance. Cell Metab. 2015 Mar 3;21(3):443-54. 
[5] Shen H, Nie J, Wang X, et al. MOTS-c relieves hepatocellular carcinoma resistance to TRAIL-induced apoptosis under hypoxic conditions by activating MEF2A[J]. Experimental Cell Research, 2025, 444(1): 114354.
[6] Yin X, Jing Y, Chen Q, et al. The intraperitoneal administration of MOTS-c produces antinociceptive and anti-inflammatory effects through the activation of AMPK pathway in the mouse formalin test[J]. European journal of pharmacology, 2020, 870: 172909.

MOTS-c是一种线粒体衍生的具有代谢调节功能的多肽 [1]。MOTS-c通过激活AMPK通路和抑制MAP激酶-c-fos信号通路发挥抗伤害和抗炎作用 [2]。MOTS-c可用于应激、炎症、代谢、神经保护和衰老方面的研究 [3]

在体外,MOTS-c(0-100μM; 8-24小时)能够以时间和剂量依赖性方式促进HEK 293细胞的AMPK(Thr 172)和Akt(Ser 473)磷酸化 [4]。不同浓度的MOTS-c(0、2.5、5、10、20和40μM; 24小时)会减弱缺氧处理对HCC细胞中DR4、DR5、FADD和caspase-8的抑制作用。MOTS-c通过激活MEF2A来减弱肝癌细胞对TRAIL诱导的细胞凋亡的抵抗 [5]

在体内,MOTS-c(5mg/kg/d; i.p.)处理雄性C57 BL/6小鼠7天,显著提高了胰岛素刺激的葡萄糖清除率,并改善了骨骼肌的胰岛素敏感性 [4]。在福尔马林处理前4小时对小鼠进行MOTS-c(50mg/kg; i.p.)治疗,显著降低了小鼠血清中促炎细胞因子水平并提高抗炎细胞因子水平。此外,MOTS-c处理显著提高了AMPKα磷酸化水平,抑制了福尔马林诱导的小鼠脊髓细胞外信号调节激酶(ERK)、c-Jun氨基末端激酶(JNK)以及P38活化和c-fos表达 [6]

实验参考方法

Cell experiment [1]:

Cell lines

HEK293 cells

Preparation Method

HEK293 cells are usually cultured in the Dulbecco-modified Eagle's Medium (DMEM). Since the main function of mitochondria involves metabolic processes, the next step is to investigate the impact of MOTS-c on cell metabolism using an unbiased global metabolomics analysis method in vitro. Using a "function-enhancing" model, studies were conducted using HEK293 cells with stable overexpression of MOTS-c (MOTS-c-ST) or with 10μM synthetic MOTS-c for 24 hours and 72 hours of exogenous treatment. Microarray analysis was performed on HEK293 cells treated with MOTS-c for 4 hours and 72 hours. The level of AICAR measured in MOTS-c-ST cells by mass spectrometry.

Reaction Conditions

10μM; 4h, 72h

Applications

MOTS-c targets the methionine-folate cycle, increases the level of AICAR, and activates AMPK.
Animal experiment [1]:

Animal models

ICR mice

Preparation Method

In all in vivo experiments, MOTS-c was injected intraperitoneally daily. Eight-week-old CD-1 (ICR) mice were purchased from Harlan Company. C57BL/6 mice were purchased from Jackson Laboratory. The mice were fed a high-fat diet (containing 60% calories) and a matched control diet for 8 weeks. The diet was changed twice a week, and body weight and food intake were recorded daily (N=10). Seven days after intraperitoneal injection of MOTS-c, a glucose tolerance test (GTT) was conducted. Subsequently, a hyperinsulinemic-euglycemic clamp test was performed to quantify the effect of 7 days of MOTS-c treatment on systemic insulin sensitivity.

Dosage form

5mg/kg/day for 7 days; i.p.

Applications

MOTS-c significantly enhanced the glucose clearance rate stimulated by insulin and improved insulin sensitivity in skeletal muscle.

References:
[1] Lee C, Zeng J, Drew BG, Sallam T, Martin-Montalvo A, Wan J, Kim SJ, Mehta H, Hevener AL, de Cabo R, Cohen P. The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance. Cell Metab. 2015 Mar 3;21(3):443-54.

化学性质

Cas No. 1627580-64-6 SDF Download SDF
分子式 C101H152N28O22S2 分子量 2174.6
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1 mM 0.4599 mL 2.2993 mL 4.5985 mL
5 mM 0.092 mL 0.4599 mL 0.9197 mL
10 mM 0.046 mL 0.2299 mL 0.4599 mL
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