Background
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].
参考文献:
[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].
en_zh_2022q2.md
Protocol
| Cell experiment [1]: |
|
Cell lines
|
Cardiomyocyte cells from 1- to 2-d-old Wistar rats
|
|
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 were activated by OA, use the
|
|
Reaction Conditions
|
1 μM for 24 hours
|
|
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]: |
|
Animal models
|
Male FVB (H-2q) and C57BL/6J (H-2b) mice
|
|
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.
|
|
Dosage form
|
osmotic pumps , 20 mg/kg/day
|
|
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
|
|
参考文献:
[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.
[2]: Koyanagi T. Noguchi K. Ootani A. Inagaki K. Robbins R.C. Mochly-Rosen D. Pharmacological inhibition of ε PKC suppresses chronic inflammation in murine cardiac transplantation model. J. Mol. Cell Cardiol. 2007; 43: 517-522
|
没有评价数据