PKCε Inhibitor Peptide
(Synonyms: Protein Kinase Cɛ Inhibitor Peptide，ɛV1-2) 目录号 : GC44655
PKCε Inhibitor Peptide，也称为 εV1-2，是一种蛋白激酶 C ε (PKCε) 衍生肽，作为选择性 PKCε 抑制剂，抑制 PKCε 的易位 。
Cas No.:182683-50-7
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
| Cell experiment [1]: | |
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Cell lines |
Cardiomyocyte cells from 1- to 2-d-old Wistar rats |
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Preparation Method |
Cells incubated with a mixture of 100 µg/ml of Oleic acid (OA) and 400 µg/ml of bovine serum albumin for 12, 24, or 48 h at 37 °C, while the control group was treated with BSA alone for 24 or 48 h. To determine which protein kinases are activated by OA, the Src kinase inhibitor PP1 (10 µM) and three PKC inhibitors, calphostin C (a general PKC inhibitor; 500 nM), Gö6976 (a PKCa inhibitor; 1 µM), and peptide eV1–2 (a PKCe inhibitor; 1 µM), were used. The cells were incubated for 24 h with inhibitor alone or with OA plus inhibitor. |
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Reaction Conditions |
1 µM for 24 hours |
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Applications |
Calphostin C blocked OA-induced Cx43 Ser368 phosphorylation, showing involvement of PKC in this signaling cascade. In addition, PKCε Inhibitor Peptide, also blocked the effect, showing that PKCε was involved. |
| Animal experiment [2]: | |
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Animal models |
Male FVB (H-2q) and C57BL/6J (H-2b) mice |
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Preparation Method |
Recipient mice were treated with PKCε Inhibitor Peptide (n = 9, 20 mg/kg/day) or with TAT as a control (13 mg/kg/day; n = 8) using 0.1 mL osmotic pumps (release rate; 0.25 µL/h, 30 mM of each peptide in sterile saline) implanted subcutaneously on day 3, replaced on day 17 and left them until 30 days after transplantation. |
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Dosage form |
osmotic pumps , 20 mg/kg/day |
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Applications |
PKCε Inhibitor Peptide treatment significantly improved the beating score of cardiac allografts compared to TAT-peptide treatment, suggesting that adding PKCε Inhibitor Peptide treatment to CyA augmented preservation of graft function without toxic side effects. The beating score in the PKCε Inhibitor Peptide treated group at 30 days was equivalent to that after 14 days in the TAT control group |
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References: [1]: Yuahn-Sieh Huang, et al. Mechanism of oleic acid-induced gap junctional disassembly in rat cardiomyocytes. J Mol Cell Cardiol. 2004 Sep;37(3):755-66. |
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PKCε Inhibitor Peptide, also called εV1-2, is a protein kinase C ε (PKCε)-derived peptide, act as a selective PKCε inhibitor, inhibits the translocation of PKCε [1]. PKCε Inhibitor Peptide is a peptide designed to compete with native nPKC ε to bind ε-Receptors for activated C Kinase (ε-RACK) and thereby inhibits nPKC ε catalytic activity due to decreased substrate accessibility.
PKCε Inhibitor Peptide, a selective PKCε inhibitor, the addition of PKCε Inhibitor Peptide interferes with the interaction between PKCε and its anchoring protein, and abolishes the cardioprotective effects of PKCε [2]. ADP-induced thromboxane generation in human platelets pretreated with PKCε Inhibitor Peptide was more compared to the platelets pretreated with control peptide [4].
PKCε Inhibitor Peptide were used to inhibit PKCε expression and activity. Apigenin-7-O-β-D-(-6"-p-coumaroyl)-glucopyranoside (APG) preconditioning-induced PKCε translocation to the mitochondria and anti-mitochondrial oxidative stress effects were attenuated by PKCε-targeted ε-V1-2 treatment in IR-injured hearts [3].
References:
[1]. M Yedovitzky, et al. Translocation inhibitors define specificity of protein kinase C isoenzymes in pancreatic beta-cells. J Biol Chem. 1997 Jan 17;272(3):1417-20.
[2]. L. Tang, Y. Peng, T. Xu, X. Yi, Y. Liu, Y. Luo, D. Yin, M. He. The effects of quercetin protect cardiomyocytes from A/R injury is related to its capability to increasing expression and activity of PK C epsilon protein.Mol. Cell. Biochem., 382 (2013), pp. 145-152
[3]. Zhu Y, Di S, Hu W, et al.. A new flavonoid glycoside (APG) isolated from Clematis tangutica attenuates myocardial ischemia/reperfusion injury via activating PKCε signaling.Biochim Biophys Acta Mol Basis Dis. 2017; 1863:701-711. doi: 10.1016/j.bbadis.2016.12.013
[4]. Yamini Saraswathy Bynagari, B-Tech., Bela Nagy, M.D., et al. nPKC Epsilon Negatively Regulates Platelet Functional Responses 2008. Blood (2008) 112 (11): 2855.
PKCε Inhibitor Peptide,也称为 εV1-2,是一种蛋白激酶 C ε (PKCε) 衍生肽,作为选择性 PKCε 抑制剂,抑制 PKCε 的易位 [1]。 PKCε 抑制肽是一种肽,旨在与天然 nPKC ε 竞争结合激活 C 激酶 (ε-RACK) 的 ε-受体,从而由于底物可及性降低而抑制 nPKC ε 催化活性。
PKCε Inhibitor Peptide,一种选择性的PKCε抑制剂,PKCε Inhibitor Peptide的加入会干扰PKCε与其锚定蛋白的相互作用,从而消除PKCε的心脏保护作用[2]。与用对照肽预处理的血小板[4]相比,用 PKCε 抑制剂肽预处理的人血小板中 ADP 诱导的血栓素生成更多。
PKCε 抑制肽用于抑制 PKCε 的表达和活性。芹菜素-7-O-β-D-(-6\-p-coumaroyl)-glucopyranoside (APG) preconditioning-induced PKCε translocation to the mitochondria and anti-mitochondrial oxidative stress effects were attenuated by PKCε-targeted ε-V1-2en_zh_2022q2.mdtreatment in IR-injured hearts [3].
| Cas No. | 182683-50-7 | SDF | |
| 别名 | Protein Kinase Cɛ Inhibitor Peptide，ɛV1-2 | ||
| Canonical SMILES | [H]N[C@@H](CCC(O)=O)C(N[C@H](C(N[C@@H](C(C)C)C(N[C@@H](CO)C(N[C@@H](CC(C)C)C(N[C@@H](CCCCN)C(N1CCC[C@H]1C(N[C@]([C@@H](C)O)([H])C(O)=O)=O)=O)=O)=O)=O)=O)C)=O | ||
| 分子式 | C37H65N9O13 | 分子量 | 844 |
| 溶解度 | 100mg/mL in DMSO | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.1848 mL | 5.9242 mL | 11.8483 mL |
| 5 mM | 0.237 mL | 1.1848 mL | 2.3697 mL |
| 10 mM | 0.1185 mL | 0.5924 mL | 1.1848 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Ethanol-Induced Changes in PKCε: From Cell to Behavior
Front Neurosci2018 Apr 12;12:244.PMID: 29706864DOI: 10.3389/fnins.2018.00244
The long-term binge intake of ethanol causes neuroadaptive changes that lead to drinkers requiring higher amounts of ethanol to experience its effects. This neuroadaptation can be partly attributed to the modulation of numerous neurotransmitter receptors by the various protein kinases C (PKCs). PKCs are enzymes that control cellular activities by regulating other proteins via phosphorylation. Among the various isoforms of PKC, PKCε is the most implicated in ethanol-induced biochemical and behavioral changes. Ethanol exposure causes changes to PKCε expression and localization in various brain regions that mediate addiction-favoring plasticity. Ethanol works in conjunction with numerous upstream kinases and second messenger activators to affect cellular PKCε expression. Chauffeur proteins, such as receptors for activated C kinase (RACKs), cause the translocation of PKCε to aberrant sites and mediate ethanol-induced changes. In this article, we aim to review the following: the general structure and function of PKCε, ethanol-induced changes in PKCε expression, the regulation of ethanol-induced PKCε activities in DAG-dependent and DAG-independent environments, the mechanisms underlying PKCε-RACKε translocation in the presence of ethanol, and the existing literature on the role of PKCε in ethanol-induced neurobehavioral changes, with the goal of creating a working model upon which further research can build.
mTORC and PKCε in Regulation of Alcohol Use Disorder
2020;20(17):1696-1708.PMID: 32579497DOI: 10.2174/1389557520666200624122325
Alcohol use disorder (AUD) is characterized by compulsive binge alcohol intake, leading to various health and social harms. Protein Kinase C epsilon (PKCε), a specific family of PKC isoenzyme, regulates binge alcohol intake, and potentiates alcohol-related cues. Alcohol via upstream kinases like the mammalian target to rapamycin complex 1 (mTORC1) or 2 (mTORC2), may affect the activities of PKCε or vice versa in AUD. mTORC2 phosphorylates PKCε at hydrophobic and turn motif, and was recently reported to be associated with alcohol-seeking behavior, suggesting the potential role of mTORC2-PKCε interactions in the pathophysiology of AUD. mTORC1 regulates translation of synaptic proteins involved in alcohol-induced plasticity. Hence, in this article, we aimed to review the molecular composition of mTORC1 and mTORC2, drugs targeting PKCε, mTORC1, and mTORC2 in AUD, upstream regulation of mTORC1 and mTORC2 in AUD and downstream cellular mechanisms of mTORCs in the pathogenesis of AUD.
Regulation of the cytokinesis cleavage furrow by PKCε
Biochem Soc Trans.2014 Dec;42(6):1534-7.PMID: 25399566DOI: 10.1042/BST20140240
Cytokinesis is the final act of the cell cycle where the replicated DNA and cellular contents are finally split into two daughter cells. This process is very tightly controlled as DNA segregation errors and cytokinesis failure is commonly associated with aneuploidy and aggressive tumours. Protein kinase Cε (PKCε) is a lipid-activated serine/threonine kinase that is part of the PKC superfamily. PKCε plays a complex role in the regulation of migration, adhesion and cytokinesis and in the present article we discuss the interplay between these processes. Integrin-mediated interaction with the actin cytoskeleton is a known regulator of cell adhesion and migration and there is emerging evidence that this pathway may also be essential for cytokinesis. We discuss evidence that a known actin-binding region in PKCε is involved in PKCε-mediated regulation of cytokinesis, providing a link between integrin-mediated stabilization of the cytokinesis furrow and PKCε recruitment..
Electroacupuncture Regulates Pain Transition Through Inhibiting PKCε and TRPV1 Expression in Dorsal Root Ganglion
Front Neurosci.2021 Jul 20;15:685715.PMID: 34354561DOI: 10.3389/fnins.2021.685715
Many cases of acute pain can be resolved with few side effects. However, some cases of acute pain may persist beyond the time required for tissue injury recovery and transit to chronic pain, which is hard to treat. The mechanisms underlying pain transition are not entirely understood, and treatment strategies are lacking. In this study, the hyperalgesic priming model was established on rats to study pain transition by injection of carrageenan (Car) and prostaglandin E2 (PGE2). The expression levels of protein kinase C epsilon (PKCε) and transient receptor potential vanilloid 1 (TRPV1) in the L4-L6 dorsal root ganglion (DRG) were investigated. Electroacupuncture (EA) is a form of acupuncture in which a small electric current is passed between a pair of acupuncture needles. EA was administrated, and its effect on hyperalgesia and PKCε and TRPV1 expression was investigated. The PKCε-TRPV1 signaling pathway in DRG was implicated in the pain transition. EA increased the pain threshold of model animals and regulated the high expression of PKCε and TRPV1. Moreover, EA also regulated hyperalgesia and high TRPV1 expression induced by selective PKCε activation. We also found that EA partly increased chronic pain threshold, even though it was only administered between the Car and PGE2 injections. These findings suggested that EA could prevent the transition from acute to chronic pain by inhibiting the PKCε and TRPV1 expression in the peripheral nervous system.
Activation of PKCε-ALDH2 Axis Prevents 4-HNE-Induced Pain in Mice
Biomolecules.2021 Nov 30;11(12):1798. PMID: 34944441DOI: 10.3390/biom11121798
Protein kinase Cε (PKCε) is highly expressed in nociceptor neurons and its activation has been reported as pro-nociceptive. Intriguingly, we previously demonstrated that activation of the mitochondrial PKCε substrate aldehyde dehydrogenase-2 (ALDH2) results in anti-nociceptive effects. ALDH2 is a major enzyme responsible for the clearance of 4-hydroxy-2-nonenal (4-HNE), an oxidative stress byproduct accumulated in inflammatory conditions and sufficient to induce pain hypersensitivity in rodents. Here we determined the contribution of the PKCε-ALDH2 axis during 4-HNE-induced mechanical hypersensitivity. Using knockout mice, we demonstrated that PKCε is essential for the nociception recovery during 4-HNE-induced hypersensitivity. We also found that ALDH2 deficient knockin mice display increased 4-HNE-induced nociceptive behavior. As proof of concept, the use of a selective peptide activator of PKCε (ΨεHSP90), which favors PKCε translocation to mitochondria and activation of PKCε-ALDH2 axis, was sufficient to block 4-HNE-induced hypersensitivity in WT, but not in ALDH2-deficient mice. Similarly, ΨεHSP90 administration prevented mechanical hypersensitivity induced by endogenous production of 4-HNE after carrageenan injection. These findings provide evidence that selective activation of mitochondrial PKCε-ALDH2 axis is important to mitigate aldehyde-mediated pain in rodents, suggesting that ΨεHSP90 and small molecules that mimic it may be a potential treatment for patients with pain.